This study was undertaken to provide a detailed account of the effect of chronic treatment with a... more This study was undertaken to provide a detailed account of the effect of chronic treatment with a small dose of caffeine on the deleterious effects of sleep loss on brain function in rats. Experimental Design: We investigated the effects of chronic (4 weeks) caffeine treatment (0.3 g/L in drinking water) on memory impairment in acutely (24 h) sleep-deprived adult male Wistar rats. Sleep deprivation was induced using the modified multiple platform model. The effects of caffeine on sleep deprivation-induced hippocampus-dependent learning and memory deficits were studied by 3 approaches: learning and memory performance in the radial arm water maze task, electrophysiological recording of early long-term potentiation (E-LTP) in area CA1 of the hippocampus, and levels of memory-and synaptic plasticity-related signaling molecules after E-LTP induction.
Journal of Pharmacology and Experimental Therapeutics
In the isolated superior cervical ganglion of the rat, activation of either DA1 or DA2 receptors ... more In the isolated superior cervical ganglion of the rat, activation of either DA1 or DA2 receptors leads to inhibition of ganglionic transmission. Using dopamine as well as relatively selective dopamine receptor agonists and antagonists we have performed electrophysiological as well as biochemical experiments to study the nature of dopamine receptors in this sympathetic ganglion. Fenoldopam, a selective DA1 receptor agonist caused marked inhibition of the compound postganglionic action potential evoked by stimulation of preganglionic nerve. The inhibitory effect of fenoldopam was antagonized by the DA1 receptor antagonist R-sulpiride but not by the DA2 receptor antagonist S-sulpiride. However, the more potent and selective DA1 receptor antagonist SCH-23390 failed to antagonize ganglion blocking effect of fenoldopam indicating that DA1 receptor in sympathetic ganglia is different from that in blood vessels. The superior cervical ganglion also contains DA2 receptors inasmuch as quinpiro...
Long-term potentiation of sympathetic ganglia (gLTP), a unique form of synaptic plasticity, is se... more Long-term potentiation of sympathetic ganglia (gLTP), a unique form of synaptic plasticity, is serotonin dependent and can be blocked with 5-HT3 receptor antagonists. Long-lasting enhancement of the basal tone of ganglionic transmission (as with gLTP) is expected to result in sustained increase in peripheral resistance that would lead to elevated blood pressure. We examined the possibility that in sympathetic ganglia, gLTP may be involved in the expression of stress-induced (neurogenic) form of hypertension. High blood pressure in spontaneously hypertensive rat (SHR), known to show exaggerated cardiovascular defense reactions to environmental stimuli, is partly due to a neurogenic factor. Chronic treatment of SHR and their normotensive counterpart, the Wistar Kyoto (WKY) rats with the 5-HT3 receptor antagonist tropisetron (ICS; 5 mg/kg/day), caused a marked decrease in the blood pressure of the SHR but not of WKY rats. Increasing the daily dose of ICS cumulatively (7 and 10 mg/kg) d...
The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP), 2006
The effect of chronic nicotine treatment on chronic psychosocial stress-induced impairment of sho... more The effect of chronic nicotine treatment on chronic psychosocial stress-induced impairment of short-term memory and long-term potentiation (LTP) was determined. An "intruder" stress model was used to induce psychosocial stress for 4-6 wk, during which rats were injected with saline or nicotine (1 mg/kg s.c.) twice a day. The radial arm water maze memory task was used to test hippocampus-dependent spatial memory. Chronic psychosocial stress impaired short-term memory without affecting the learning phase or long-term memory. Concurrent chronic nicotine treatment prevented stress-induced short-term memory impairment. In normal rats chronic nicotine treatment had no effect on learning and memory. Extracellular recordings from the CA1 region of anaesthetized rats showed severe reduction of LTP magnitude in stressed rats, which was normalized in nicotine-treated stressed rats. Nicotine had no effect on LTP in control animals. These results showed that chronic nicotine treatment ...
The Journal of pharmacology and experimental therapeutics, 1982
Alterations by ketamine (10-100 microM) and ditran (50-100 microM) of end-plate currents were stu... more Alterations by ketamine (10-100 microM) and ditran (50-100 microM) of end-plate currents were studied using transected cutaneous pectoris muscles. Both drugs reduced peak current and shortened the time constant for end-plate current decay (tau). Ketamine was more effective at pH 5.3 than at 7.4 or 9.1. Recovery from blockade was asymmetrical in that tau recovered more quickly than did peak current when the drugs were removed from the bath. By contrast, 4-aminopyridine antagonized the depression of peak current by ketamine, but not the reduction of tau. Both ketamine and ditran disrupted the voltage dependence of tau. The binding to microsacs prepared from electric organs of [3H]phencyclidine ([3H]PCP) was blocked by ketamine and ditran. In microsacs treated with carbachol, the IC50 for ketamine block of [3H]PCP binding was 6.6 X 10(-6) M. For ditran, the IC50 for block of [3H]PCP binding in the presence of carbachol was 1.7 X 10(-6) M. The binding of [alpha-125I]bungarotoxin to the ...
The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP), 2012
In Alzheimer's disease (AD), progressive accumulation of β-amyloid (Aβ) peptides impairs nico... more In Alzheimer's disease (AD), progressive accumulation of β-amyloid (Aβ) peptides impairs nicotinic acetylcholine receptor (nAChR) function by a mechanism that may involve α7 and α4β2-nAChR subtypes. Additionally, the beta-site amyloid precursor protein (APP)-cleaving enzyme (BACE), the rate-limiting enzyme in the pathogenic Aβ production pathway, is expressed at high levels in hippocampal and cortical regions of AD brains. We measured hippocampal area CA1 protein levels of BACE and α7- and α4β2-nAChR subunits using an Aβ rat model of AD (14-d osmotic pump i.c.v. infusion of 300 pmol/d Aβ peptides) in the presence and absence of chronic stress and/or chronic nicotine treatment. There was a significant increase in the levels of BACE in Aβ-infused rats, which were markedly intensified by chronic (4-6 wk) stress, but were normalized in Aβ rats chronically treated with nicotine (1 mg/kg b.i.d.). The levels of the three subunits α7, α4 and β2 were significantly decreased in Aβ rats, b...
The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP), 2013
We have previously shown that nicotine prevents stress-induced memory impairment. In this study, ... more We have previously shown that nicotine prevents stress-induced memory impairment. In this study, we have investigated the role of α7- and α4β2-nicotinic acetylcholine receptors (nAChRs) in the protective effect of nicotine during chronic stress conditions. Chronic psychosocial stress was induced using a form of rat intruder model. During stress, specific antagonist for either α7-nAChRs [methyllycaconitine (MLA)] or α4β2-nAChRs [dihydro-β-erythroidine (DHβE)] was infused into the hippocampus using a 4-wk osmotic pump at a rate of 82 μg/side.d and 41 μg/side.d, respectively. Three weeks after the start of infusion, all rats were subjected to a series of cognitive tests in the radial arm water maze (RAWM) for six consecutive days or until the animal reached days to criterion (DTC) in the fourth acquisition trial and in all memory tests. DTC is defined as the number of days the animal takes to make no more than one error in three consecutive days. In the short-term memory test, MLA-infu...
The International Journal of Neuropsychopharmacology, 2013
Previously, we reported that in a rat model of sporadic Alzheimer's disease (AD) generated by exo... more Previously, we reported that in a rat model of sporadic Alzheimer's disease (AD) generated by exogenous administration of Aβ 1-42 (250 pmol/d for 2 wk) via mini-osmotic pump, the animals exhibited learning and memory impairment, which could be attributed to the deleterious alterations in the levels of cognition-related signalling molecules. We showed that 4 wk of treadmill exercise totally prevented these impairments. Here, we evaluated the effect of exercise on non-cognitive function and basal synaptic transmission in the Cornu Ammonis 1 (CA1) area using the same AD model. Our results indicated that the anxiety behaviour of Aβ-treated rats was prevented by 4 wk of treadmill exercise. Exercised/Aβ-infused rats spent a longer time in the centre area of the open field (OF), elevated plus maze (EPM) paradigms and the light area of the light-dark (LD) box, which were similar to those of control and exercise rats. Furthermore, under basal conditions the aberrant up-regulation of calcineurin (PP2B) and reduction of phosphorylated Ca 2+ /calmodulin dependent protein kinase II (p-CaMKII) levels induced by AD-like pathology were normalised by the exercise regimen. We conclude that regular exercise may exert beneficial effects on both cognitive and non-cognitive functions in this AD model.
Although the physiological function of sleep is not completely understood, it is well documented ... more Although the physiological function of sleep is not completely understood, it is well documented that it contributes significantly to the process of learning and memory. Ample evidence suggests that adequate sleep is essential for fostering connections among neuronal networks for memory consolidation in the hippocampus. Sleep deprivation studies are extremely valuable in understanding why we sleep and what are the consequences of sleep loss. Experimental sleep deprivation in animals allows us to gain insight into the mechanism of sleep at levels not possible to study in human subjects. Many useful approaches have been utilized to evaluate the effect of sleep loss on cognitive function, each with relative advantages and disadvantages. In this review we discuss sleep and the detrimental effects of sleep deprivation mostly in experimental animals. The negative effects of sleep deprivation on various aspects of brain function including learning and memory, synaptic plasticity and the state of cognition-related signaling molecules are discussed.
The purpose of this hot topic issue of Current Neuropharmacology is to provide a platform to disc... more The purpose of this hot topic issue of Current Neuropharmacology is to provide a platform to discuss current knowledge regarding oxidative stress as a contributing/causal factor to the pathophysiology of psychiatric illnesses, including schizophrenia, depression, and anxiety. A better understanding of this mechanism may open new venues for prevention and treatment strategies. Due to the lack of a systematic evaluation of the role of oxidative stress in psychiatric illnesses and given the exciting new findings, this special issue is quite topical. The special issue pulls together investigators who use diverse, but complementary, approaches to study role of oxidative stress in mental health. We have assembled a team of notable experts in the field who utilize complementary approaches to study this aspect. These experts have commented on the current state of knowledge regarding the significance of oxidative stress to mental health and also point towards promising new directions potentially amenable to pharmacological intervention.
We have shown previously that chronic nicotine treatment reverses adult-onset hypothyroidism-indu... more We have shown previously that chronic nicotine treatment reverses adult-onset hypothyroidism-induced impairment of latephase long-term potentiation (L-LTP) in area CA1 of the hippocampus. In the present study, basal and stimulated levels of signaling molecules essential for the expression of L-LTP were determined in area CA1. Immunoblots analysis showed that chronic nicotine treatment of hypothyroid rats prevented the reduction in the basal protein levels of adenylyl cyclase I (ACI), mitogen-activated protein kinases [MAPKp44/42 (ERK1/ 2)], calcium-calmodulin-dependent protein kinase IV (CaMKIV), and cyclic-AMP response element binding protein [CREB; phosphorylated (P-) and total]. A significant increase in the levels of P-CREB, P-MAPKp44, P-MAPKp42 and brain derived neurotrophic factor (BDNF) was seen 4 h after multiple train high frequency stimulation (MHFS) in nicotine-treated hypothyroid and control animals, but not in hypothyroid animals. The levels of total CREB, total MAPKp44, total MAPKp42, and CaMKIV were elevated in all groups 4 h after MHFS. These findings suggest that prevention of the reduced basal level of CaMKIV, MAPKp44/42, and CREB by nicotine along with the regained ability of MHFS to induce MAPKp44/42 and CREB phosphorylation in nicotine treated hypothyroid animals may be responsible for the reversal of L-LTP impairment by chronic nicotine treatment in this disease model. V V C 2007 Wiley-Liss, Inc.
Although it is generally agreed that Ab contributes to the pathogenesis of AD, its precise role i... more Although it is generally agreed that Ab contributes to the pathogenesis of AD, its precise role in AD and the reason for the varying intensity and time of onset of the disease have not been elucidated. In addition to genetic factors, environmental issues such as stress may also play a critical role in the etiology of AD. This study examined the effect of chronic psychosocial stress in an at-risk (treatment with a subpathogenic dose of Ab; ''subAb'') rat model of AD on long-term memory by three techniques: memory tests in the radial arm water maze, electrophysiological recordings of synaptic plasticity in anesthetized rats, and immunoblot analysis of learning-and long-term memory-related signaling molecules. Chronic psychosocial stress was induced using a rat intruder model. The subAb rat model of AD was induced by continuous infusion of 160 pmol/day Ab 1-42 via a 14-day i.c.v. osmotic pump. All tests showed that subAb rats were not different from control rats. Result from behavioral tests and electrophysiological recordings showed that infusion of subAb in chronically stressed rats (stress/subAb group) caused significant impairment of cognitive functions and late-phase long-term potentiation (L-LTP). Molecular analysis of various signaling molecules after expression of L-LTP, revealed an increase in the levels of p-CREB in control, stress, and subAb rats, but not in the stress/subAb rats. These findings suggest that the chronic stress-induced molecular alteration may accelerate the impairment of cognition and synaptic plasticity in individuals ''at-risk'' for AD. V V C 2010 Wiley-Liss, Inc.
We have recently shown that chronic nicotine treatment reverses hypothyroidism-induced learning a... more We have recently shown that chronic nicotine treatment reverses hypothyroidism-induced learning and memory impairment. Chronic nicotine treatment also reverses the hypothyroidism-induced impairment of long-term potentiation (LTP). Analysis of LTP associated key signaling molecules revealed that chronic nicotine treatment prevented the hypothyroidism-induced reduction of the basal phosphotransferase activity of CaMKII and protein levels of P-CaMKII. In addition, the failure of high frequency stimulation to increase the levels of P-CaMKII in hypothyroid rats was reversed by nicotine treatment, suggesting that the neuroprotective effect of nicotine during hypothyroidism involved activation of CaMKII. Furthermore, chronic nicotine treatment reverses the hypothyroidism-induced elevated phosphatase activity and protein levels of calcineurin, a phosphatase that regulates CaMKII activation. We conclude that the neuroprotective effects of nicotine in adult-onset hypothyroidism may result from restoration of CaMKII and calcineurin activity. V V C 2006 Wiley-Liss, Inc.
Hypothyroidism impairs early long-term potentiation (LTP) in the CA1 but not in the dentate gyrus... more Hypothyroidism impairs early long-term potentiation (LTP) in the CA1 but not in the dentate gyrus (DG) of hippocampus of anesthetized adult rats. Protein levels and activities of signaling molecules in both the CA1 and DG of surgically thyroidectomized and shamoperated euthyroid rats were measured. Basal levels of total calmodulin kinase II (CaMKII) protein in both the CA1 and DG were decreased in hypothyroidism. Marked reduction of basal P-CaMKII levels and CaMKII activity was seen in CA1, but not in the DG of the same hypothyroid animals. Basal levels of calmodulin and protein kinase Cg (PKCg) were decreased in CA1 but remained unchanged in the DG of hypothyroid rats. Basal calcineurin levels and activity, although enhanced in CA1, were reduced in the DG of hypothyroid rats. These findings suggest that the DG may possess a compensatory mechanism whereby calcineurin levels are reduced, to allow sufficient CaMKII activity to produce an apparently normal LTP in hypothyroid rats. ' 2005 Wiley-Liss, Inc.
Rapid eye movement (REM) sleep deprivation (SD) is implicated in impairment of spatial learning a... more Rapid eye movement (REM) sleep deprivation (SD) is implicated in impairment of spatial learning and memory and hippocampal long-term potentiation (LTP). An increase in nicotine consumption among habitual smokers and initiation of tobacco use by nonsmokers was observed during SD. Although nicotine treatment was reported to attenuate the impairment of learning and memory and LTP associated with several mental disorders, the effect of nicotine on SD-induced learning and memory impairment has not been studied. Modified multiple platform paradigm was used to induce SD for 24 or 48 h during which rats were injected with saline or nicotine (1 mg kg 21 s.c.) twice a day. In the radial arm water maze (RAWM) task, 24-or 48-h SD significantly impaired learning and short-term memory. In addition, extracellular recordings from CA1 and dentate gyrus (DG) regions of the hippocampus in urethane anesthetized rats showed a significant impairment of LTP after 24-and 48-h SD. Treatment of normal rats with nicotine for 24 or 48 h did not enhance spatial learning and memory or affect magnitude of LTP in the CA1 and DG regions. However, concurrent, acute treatment of rats with nicotine significantly attenuated SDinduced impairment of learning and STM and prevented SD-induced impairment of LTP in the CA1 and DG regions. These results show that acute nicotine treatment prevented the deleterious effect of sleep loss on cognitive abilities and synaptic plasticity. V V C 2010 Wiley-Liss, Inc.
The present study aimed to investigate the effects of treadmill exercise on sleep deprivation (S-... more The present study aimed to investigate the effects of treadmill exercise on sleep deprivation (S-D)-induced impairment of hippocampal dependent long-term memory, late phase long-term potentiation (L-LTP) and its signaling cascade in the cornu ammonis 1 (CA1) area.
Moderate treadmill exercise rescues anxiety and depression-like 2 behavior as well as memory impa... more Moderate treadmill exercise rescues anxiety and depression-like 2 behavior as well as memory impairment in a rat model of posttraumatic 3 stress disorder ☆ 4 Gaurav Q1 • Single-prolonged stress (SPS)-induced behavioral and cognitive impairments in rats 10 • Moderate treadmill exercise rescued SPS-induced behavioral and cognitive impairments in rats 11 12 1 3 a b s t r a c t 1 4 traumatic stress disorder (PTSD) is a condition which can develop from exposure to a severe traumatic 28 event such as those occurring during wars or natural disasters. Benzodiazepines and selective serotonin reuptake 29 inhibitors (SSRIs) are considered the gold standard for PTSD treatment, but their side effects pose a serious prob-30 lem. While regular physical exercise is regarded as a mood elevator and known to enhance cognitive function, its 31 direct role in rescuing core symptoms of PTSD including anxiety and depression-like behaviors and cognitive im-32 pairment is unclear. In the present study using the single-prolonged stress (SPS) rat model of PTSD (2 h restrain, 33 20 min forced swimming, 15 min rest, and 1-2 min diethyl ether exposure), we examined the beneficial effect of 34 moderate treadmill exercise on SPS-induced behavioral deficits including anxiety and depression-like behaviors 35 and memory impairment. Male Wistar rats were randomly assigned into four groups: control (sedentary), 36 exercised, SPS (no exercise), or SPS-exercised. Rats were exercised on a rodent treadmill for 14 consecutive 37 days. Rats in all groups were tested for anxiety-like behaviors using open field (OF), light-dark and elevated-38 plus maze tests. All rats were tested for short-term and long-term memory in the radial arm water maze test. 39 Rats were then sacrificed, blood was collected (for corticosterone levels), and individual organs (spleen, adrenals, 40 and thymus) harvested. Results suggest that moderate physical exercise ameliorates SPS-induced behavioral def-41 icits in rats. 42 Please cite this article as: Patki G, et al, Moderate treadmill exercise rescues anxiety and depression-like behavior as well as memory impairment in a rat model of posttraumatic stress disorder, Physiol Behav (2014), http://dx.(psychological), 20 min forced swim (physical) and ether anesthesia 77 (endocrinological), respectively. Application of these stresses increases 78 serum corticosterone levels, and by combining three different kinds of 79 stresses, the SPS model could accomplish severity of symptoms analo-80 gous to that of PTSD [10,11]. Studies have shown that rats that undergo 81 the SPS procedure suffer from increased anxiety and impairment of 82 social and object recognition memory [12] and present with changes 83 in glucocorticoid and mineralocorticoid receptors involved in the 84 HPA system [13,14]. Extensive evidence shows that regular exercise 85 is beneficial in ameliorating memory impairment, enhancing cogni-86 tive function and preventing memory decline [15,16]. Therefore, 87 exercise may be beneficial in reversing PTSD-induced symptoms in-88 cluding anxiety and depressive behaviors and learning and memory 89 function impairment [17]. Statistics show that individuals who suffer 90 from PTSD tend, on an average, to exercise less (including activities 91 such as shopping, walking, and sports) compared to before the onset 92 of the disorder [18,19]. Patients also reported poor compliance to 93 medication [19]. 94 In the present study we used the SPS rat model of PTSD to study the 95 effect of regular exercise as a potential non-pharmacological therapeu-96 tic approach for attenuating SPS-induced deficits including anxiety-97 like (anxiety), depression-like (depression) behaviors, and learning 98 and memory function impairment. 99 2. Materials and methods 100 2.1. Animals 101 Male Wistar rats (175-200 g; Charles River, Wilmington, MA) were 102 housed with a 12-h light, 12-h dark cycle (lights on at 0600 h) in a 103 climate-controlled room with ad libitum food and water. After arrival 104 at the research facility, all rats were allowed 1 week to acclimate before 105 manipulations began (Scheme 1). All experiments were conducted in 106 accordance with the NIH guidelines using approved protocols from 107 the University of Houston Animal Care Committee. 108 2.2. Single-prolonged stress model 109 Male Wistar rats were assigned into 4 groups; group 1: control, 110 group 2: SPS, group 3: exercised, group 4: SPS-exercised. 111 Single prolonged stress (SPS): The two SPS groups: SPS and exercise 112 SPS rats (10 rats/group) were subjected to a one time combined stress 113 paradigm applied consecutively in a day [9,20]: immobilization 114 (compression with double layered plastic Ziploc bag with edges cov-115 ered in duct tape to prevent the rats from escaping and also an open-116 ing for the rat nose was provided in the Ziploc bag) for 2 h followed 117 immediately by 20 min of forced swimming (in a tall cylindrical tank 118
This study was undertaken to provide a detailed account of the effect of chronic treatment with a... more This study was undertaken to provide a detailed account of the effect of chronic treatment with a small dose of caffeine on the deleterious effects of sleep loss on brain function in rats. Experimental Design: We investigated the effects of chronic (4 weeks) caffeine treatment (0.3 g/L in drinking water) on memory impairment in acutely (24 h) sleep-deprived adult male Wistar rats. Sleep deprivation was induced using the modified multiple platform model. The effects of caffeine on sleep deprivation-induced hippocampus-dependent learning and memory deficits were studied by 3 approaches: learning and memory performance in the radial arm water maze task, electrophysiological recording of early long-term potentiation (E-LTP) in area CA1 of the hippocampus, and levels of memory-and synaptic plasticity-related signaling molecules after E-LTP induction.
Journal of Pharmacology and Experimental Therapeutics
In the isolated superior cervical ganglion of the rat, activation of either DA1 or DA2 receptors ... more In the isolated superior cervical ganglion of the rat, activation of either DA1 or DA2 receptors leads to inhibition of ganglionic transmission. Using dopamine as well as relatively selective dopamine receptor agonists and antagonists we have performed electrophysiological as well as biochemical experiments to study the nature of dopamine receptors in this sympathetic ganglion. Fenoldopam, a selective DA1 receptor agonist caused marked inhibition of the compound postganglionic action potential evoked by stimulation of preganglionic nerve. The inhibitory effect of fenoldopam was antagonized by the DA1 receptor antagonist R-sulpiride but not by the DA2 receptor antagonist S-sulpiride. However, the more potent and selective DA1 receptor antagonist SCH-23390 failed to antagonize ganglion blocking effect of fenoldopam indicating that DA1 receptor in sympathetic ganglia is different from that in blood vessels. The superior cervical ganglion also contains DA2 receptors inasmuch as quinpiro...
Long-term potentiation of sympathetic ganglia (gLTP), a unique form of synaptic plasticity, is se... more Long-term potentiation of sympathetic ganglia (gLTP), a unique form of synaptic plasticity, is serotonin dependent and can be blocked with 5-HT3 receptor antagonists. Long-lasting enhancement of the basal tone of ganglionic transmission (as with gLTP) is expected to result in sustained increase in peripheral resistance that would lead to elevated blood pressure. We examined the possibility that in sympathetic ganglia, gLTP may be involved in the expression of stress-induced (neurogenic) form of hypertension. High blood pressure in spontaneously hypertensive rat (SHR), known to show exaggerated cardiovascular defense reactions to environmental stimuli, is partly due to a neurogenic factor. Chronic treatment of SHR and their normotensive counterpart, the Wistar Kyoto (WKY) rats with the 5-HT3 receptor antagonist tropisetron (ICS; 5 mg/kg/day), caused a marked decrease in the blood pressure of the SHR but not of WKY rats. Increasing the daily dose of ICS cumulatively (7 and 10 mg/kg) d...
The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP), 2006
The effect of chronic nicotine treatment on chronic psychosocial stress-induced impairment of sho... more The effect of chronic nicotine treatment on chronic psychosocial stress-induced impairment of short-term memory and long-term potentiation (LTP) was determined. An "intruder" stress model was used to induce psychosocial stress for 4-6 wk, during which rats were injected with saline or nicotine (1 mg/kg s.c.) twice a day. The radial arm water maze memory task was used to test hippocampus-dependent spatial memory. Chronic psychosocial stress impaired short-term memory without affecting the learning phase or long-term memory. Concurrent chronic nicotine treatment prevented stress-induced short-term memory impairment. In normal rats chronic nicotine treatment had no effect on learning and memory. Extracellular recordings from the CA1 region of anaesthetized rats showed severe reduction of LTP magnitude in stressed rats, which was normalized in nicotine-treated stressed rats. Nicotine had no effect on LTP in control animals. These results showed that chronic nicotine treatment ...
The Journal of pharmacology and experimental therapeutics, 1982
Alterations by ketamine (10-100 microM) and ditran (50-100 microM) of end-plate currents were stu... more Alterations by ketamine (10-100 microM) and ditran (50-100 microM) of end-plate currents were studied using transected cutaneous pectoris muscles. Both drugs reduced peak current and shortened the time constant for end-plate current decay (tau). Ketamine was more effective at pH 5.3 than at 7.4 or 9.1. Recovery from blockade was asymmetrical in that tau recovered more quickly than did peak current when the drugs were removed from the bath. By contrast, 4-aminopyridine antagonized the depression of peak current by ketamine, but not the reduction of tau. Both ketamine and ditran disrupted the voltage dependence of tau. The binding to microsacs prepared from electric organs of [3H]phencyclidine ([3H]PCP) was blocked by ketamine and ditran. In microsacs treated with carbachol, the IC50 for ketamine block of [3H]PCP binding was 6.6 X 10(-6) M. For ditran, the IC50 for block of [3H]PCP binding in the presence of carbachol was 1.7 X 10(-6) M. The binding of [alpha-125I]bungarotoxin to the ...
The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP), 2012
In Alzheimer's disease (AD), progressive accumulation of β-amyloid (Aβ) peptides impairs nico... more In Alzheimer's disease (AD), progressive accumulation of β-amyloid (Aβ) peptides impairs nicotinic acetylcholine receptor (nAChR) function by a mechanism that may involve α7 and α4β2-nAChR subtypes. Additionally, the beta-site amyloid precursor protein (APP)-cleaving enzyme (BACE), the rate-limiting enzyme in the pathogenic Aβ production pathway, is expressed at high levels in hippocampal and cortical regions of AD brains. We measured hippocampal area CA1 protein levels of BACE and α7- and α4β2-nAChR subunits using an Aβ rat model of AD (14-d osmotic pump i.c.v. infusion of 300 pmol/d Aβ peptides) in the presence and absence of chronic stress and/or chronic nicotine treatment. There was a significant increase in the levels of BACE in Aβ-infused rats, which were markedly intensified by chronic (4-6 wk) stress, but were normalized in Aβ rats chronically treated with nicotine (1 mg/kg b.i.d.). The levels of the three subunits α7, α4 and β2 were significantly decreased in Aβ rats, b...
The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP), 2013
We have previously shown that nicotine prevents stress-induced memory impairment. In this study, ... more We have previously shown that nicotine prevents stress-induced memory impairment. In this study, we have investigated the role of α7- and α4β2-nicotinic acetylcholine receptors (nAChRs) in the protective effect of nicotine during chronic stress conditions. Chronic psychosocial stress was induced using a form of rat intruder model. During stress, specific antagonist for either α7-nAChRs [methyllycaconitine (MLA)] or α4β2-nAChRs [dihydro-β-erythroidine (DHβE)] was infused into the hippocampus using a 4-wk osmotic pump at a rate of 82 μg/side.d and 41 μg/side.d, respectively. Three weeks after the start of infusion, all rats were subjected to a series of cognitive tests in the radial arm water maze (RAWM) for six consecutive days or until the animal reached days to criterion (DTC) in the fourth acquisition trial and in all memory tests. DTC is defined as the number of days the animal takes to make no more than one error in three consecutive days. In the short-term memory test, MLA-infu...
The International Journal of Neuropsychopharmacology, 2013
Previously, we reported that in a rat model of sporadic Alzheimer's disease (AD) generated by exo... more Previously, we reported that in a rat model of sporadic Alzheimer's disease (AD) generated by exogenous administration of Aβ 1-42 (250 pmol/d for 2 wk) via mini-osmotic pump, the animals exhibited learning and memory impairment, which could be attributed to the deleterious alterations in the levels of cognition-related signalling molecules. We showed that 4 wk of treadmill exercise totally prevented these impairments. Here, we evaluated the effect of exercise on non-cognitive function and basal synaptic transmission in the Cornu Ammonis 1 (CA1) area using the same AD model. Our results indicated that the anxiety behaviour of Aβ-treated rats was prevented by 4 wk of treadmill exercise. Exercised/Aβ-infused rats spent a longer time in the centre area of the open field (OF), elevated plus maze (EPM) paradigms and the light area of the light-dark (LD) box, which were similar to those of control and exercise rats. Furthermore, under basal conditions the aberrant up-regulation of calcineurin (PP2B) and reduction of phosphorylated Ca 2+ /calmodulin dependent protein kinase II (p-CaMKII) levels induced by AD-like pathology were normalised by the exercise regimen. We conclude that regular exercise may exert beneficial effects on both cognitive and non-cognitive functions in this AD model.
Although the physiological function of sleep is not completely understood, it is well documented ... more Although the physiological function of sleep is not completely understood, it is well documented that it contributes significantly to the process of learning and memory. Ample evidence suggests that adequate sleep is essential for fostering connections among neuronal networks for memory consolidation in the hippocampus. Sleep deprivation studies are extremely valuable in understanding why we sleep and what are the consequences of sleep loss. Experimental sleep deprivation in animals allows us to gain insight into the mechanism of sleep at levels not possible to study in human subjects. Many useful approaches have been utilized to evaluate the effect of sleep loss on cognitive function, each with relative advantages and disadvantages. In this review we discuss sleep and the detrimental effects of sleep deprivation mostly in experimental animals. The negative effects of sleep deprivation on various aspects of brain function including learning and memory, synaptic plasticity and the state of cognition-related signaling molecules are discussed.
The purpose of this hot topic issue of Current Neuropharmacology is to provide a platform to disc... more The purpose of this hot topic issue of Current Neuropharmacology is to provide a platform to discuss current knowledge regarding oxidative stress as a contributing/causal factor to the pathophysiology of psychiatric illnesses, including schizophrenia, depression, and anxiety. A better understanding of this mechanism may open new venues for prevention and treatment strategies. Due to the lack of a systematic evaluation of the role of oxidative stress in psychiatric illnesses and given the exciting new findings, this special issue is quite topical. The special issue pulls together investigators who use diverse, but complementary, approaches to study role of oxidative stress in mental health. We have assembled a team of notable experts in the field who utilize complementary approaches to study this aspect. These experts have commented on the current state of knowledge regarding the significance of oxidative stress to mental health and also point towards promising new directions potentially amenable to pharmacological intervention.
We have shown previously that chronic nicotine treatment reverses adult-onset hypothyroidism-indu... more We have shown previously that chronic nicotine treatment reverses adult-onset hypothyroidism-induced impairment of latephase long-term potentiation (L-LTP) in area CA1 of the hippocampus. In the present study, basal and stimulated levels of signaling molecules essential for the expression of L-LTP were determined in area CA1. Immunoblots analysis showed that chronic nicotine treatment of hypothyroid rats prevented the reduction in the basal protein levels of adenylyl cyclase I (ACI), mitogen-activated protein kinases [MAPKp44/42 (ERK1/ 2)], calcium-calmodulin-dependent protein kinase IV (CaMKIV), and cyclic-AMP response element binding protein [CREB; phosphorylated (P-) and total]. A significant increase in the levels of P-CREB, P-MAPKp44, P-MAPKp42 and brain derived neurotrophic factor (BDNF) was seen 4 h after multiple train high frequency stimulation (MHFS) in nicotine-treated hypothyroid and control animals, but not in hypothyroid animals. The levels of total CREB, total MAPKp44, total MAPKp42, and CaMKIV were elevated in all groups 4 h after MHFS. These findings suggest that prevention of the reduced basal level of CaMKIV, MAPKp44/42, and CREB by nicotine along with the regained ability of MHFS to induce MAPKp44/42 and CREB phosphorylation in nicotine treated hypothyroid animals may be responsible for the reversal of L-LTP impairment by chronic nicotine treatment in this disease model. V V C 2007 Wiley-Liss, Inc.
Although it is generally agreed that Ab contributes to the pathogenesis of AD, its precise role i... more Although it is generally agreed that Ab contributes to the pathogenesis of AD, its precise role in AD and the reason for the varying intensity and time of onset of the disease have not been elucidated. In addition to genetic factors, environmental issues such as stress may also play a critical role in the etiology of AD. This study examined the effect of chronic psychosocial stress in an at-risk (treatment with a subpathogenic dose of Ab; ''subAb'') rat model of AD on long-term memory by three techniques: memory tests in the radial arm water maze, electrophysiological recordings of synaptic plasticity in anesthetized rats, and immunoblot analysis of learning-and long-term memory-related signaling molecules. Chronic psychosocial stress was induced using a rat intruder model. The subAb rat model of AD was induced by continuous infusion of 160 pmol/day Ab 1-42 via a 14-day i.c.v. osmotic pump. All tests showed that subAb rats were not different from control rats. Result from behavioral tests and electrophysiological recordings showed that infusion of subAb in chronically stressed rats (stress/subAb group) caused significant impairment of cognitive functions and late-phase long-term potentiation (L-LTP). Molecular analysis of various signaling molecules after expression of L-LTP, revealed an increase in the levels of p-CREB in control, stress, and subAb rats, but not in the stress/subAb rats. These findings suggest that the chronic stress-induced molecular alteration may accelerate the impairment of cognition and synaptic plasticity in individuals ''at-risk'' for AD. V V C 2010 Wiley-Liss, Inc.
We have recently shown that chronic nicotine treatment reverses hypothyroidism-induced learning a... more We have recently shown that chronic nicotine treatment reverses hypothyroidism-induced learning and memory impairment. Chronic nicotine treatment also reverses the hypothyroidism-induced impairment of long-term potentiation (LTP). Analysis of LTP associated key signaling molecules revealed that chronic nicotine treatment prevented the hypothyroidism-induced reduction of the basal phosphotransferase activity of CaMKII and protein levels of P-CaMKII. In addition, the failure of high frequency stimulation to increase the levels of P-CaMKII in hypothyroid rats was reversed by nicotine treatment, suggesting that the neuroprotective effect of nicotine during hypothyroidism involved activation of CaMKII. Furthermore, chronic nicotine treatment reverses the hypothyroidism-induced elevated phosphatase activity and protein levels of calcineurin, a phosphatase that regulates CaMKII activation. We conclude that the neuroprotective effects of nicotine in adult-onset hypothyroidism may result from restoration of CaMKII and calcineurin activity. V V C 2006 Wiley-Liss, Inc.
Hypothyroidism impairs early long-term potentiation (LTP) in the CA1 but not in the dentate gyrus... more Hypothyroidism impairs early long-term potentiation (LTP) in the CA1 but not in the dentate gyrus (DG) of hippocampus of anesthetized adult rats. Protein levels and activities of signaling molecules in both the CA1 and DG of surgically thyroidectomized and shamoperated euthyroid rats were measured. Basal levels of total calmodulin kinase II (CaMKII) protein in both the CA1 and DG were decreased in hypothyroidism. Marked reduction of basal P-CaMKII levels and CaMKII activity was seen in CA1, but not in the DG of the same hypothyroid animals. Basal levels of calmodulin and protein kinase Cg (PKCg) were decreased in CA1 but remained unchanged in the DG of hypothyroid rats. Basal calcineurin levels and activity, although enhanced in CA1, were reduced in the DG of hypothyroid rats. These findings suggest that the DG may possess a compensatory mechanism whereby calcineurin levels are reduced, to allow sufficient CaMKII activity to produce an apparently normal LTP in hypothyroid rats. ' 2005 Wiley-Liss, Inc.
Rapid eye movement (REM) sleep deprivation (SD) is implicated in impairment of spatial learning a... more Rapid eye movement (REM) sleep deprivation (SD) is implicated in impairment of spatial learning and memory and hippocampal long-term potentiation (LTP). An increase in nicotine consumption among habitual smokers and initiation of tobacco use by nonsmokers was observed during SD. Although nicotine treatment was reported to attenuate the impairment of learning and memory and LTP associated with several mental disorders, the effect of nicotine on SD-induced learning and memory impairment has not been studied. Modified multiple platform paradigm was used to induce SD for 24 or 48 h during which rats were injected with saline or nicotine (1 mg kg 21 s.c.) twice a day. In the radial arm water maze (RAWM) task, 24-or 48-h SD significantly impaired learning and short-term memory. In addition, extracellular recordings from CA1 and dentate gyrus (DG) regions of the hippocampus in urethane anesthetized rats showed a significant impairment of LTP after 24-and 48-h SD. Treatment of normal rats with nicotine for 24 or 48 h did not enhance spatial learning and memory or affect magnitude of LTP in the CA1 and DG regions. However, concurrent, acute treatment of rats with nicotine significantly attenuated SDinduced impairment of learning and STM and prevented SD-induced impairment of LTP in the CA1 and DG regions. These results show that acute nicotine treatment prevented the deleterious effect of sleep loss on cognitive abilities and synaptic plasticity. V V C 2010 Wiley-Liss, Inc.
The present study aimed to investigate the effects of treadmill exercise on sleep deprivation (S-... more The present study aimed to investigate the effects of treadmill exercise on sleep deprivation (S-D)-induced impairment of hippocampal dependent long-term memory, late phase long-term potentiation (L-LTP) and its signaling cascade in the cornu ammonis 1 (CA1) area.
Moderate treadmill exercise rescues anxiety and depression-like 2 behavior as well as memory impa... more Moderate treadmill exercise rescues anxiety and depression-like 2 behavior as well as memory impairment in a rat model of posttraumatic 3 stress disorder ☆ 4 Gaurav Q1 • Single-prolonged stress (SPS)-induced behavioral and cognitive impairments in rats 10 • Moderate treadmill exercise rescued SPS-induced behavioral and cognitive impairments in rats 11 12 1 3 a b s t r a c t 1 4 traumatic stress disorder (PTSD) is a condition which can develop from exposure to a severe traumatic 28 event such as those occurring during wars or natural disasters. Benzodiazepines and selective serotonin reuptake 29 inhibitors (SSRIs) are considered the gold standard for PTSD treatment, but their side effects pose a serious prob-30 lem. While regular physical exercise is regarded as a mood elevator and known to enhance cognitive function, its 31 direct role in rescuing core symptoms of PTSD including anxiety and depression-like behaviors and cognitive im-32 pairment is unclear. In the present study using the single-prolonged stress (SPS) rat model of PTSD (2 h restrain, 33 20 min forced swimming, 15 min rest, and 1-2 min diethyl ether exposure), we examined the beneficial effect of 34 moderate treadmill exercise on SPS-induced behavioral deficits including anxiety and depression-like behaviors 35 and memory impairment. Male Wistar rats were randomly assigned into four groups: control (sedentary), 36 exercised, SPS (no exercise), or SPS-exercised. Rats were exercised on a rodent treadmill for 14 consecutive 37 days. Rats in all groups were tested for anxiety-like behaviors using open field (OF), light-dark and elevated-38 plus maze tests. All rats were tested for short-term and long-term memory in the radial arm water maze test. 39 Rats were then sacrificed, blood was collected (for corticosterone levels), and individual organs (spleen, adrenals, 40 and thymus) harvested. Results suggest that moderate physical exercise ameliorates SPS-induced behavioral def-41 icits in rats. 42 Please cite this article as: Patki G, et al, Moderate treadmill exercise rescues anxiety and depression-like behavior as well as memory impairment in a rat model of posttraumatic stress disorder, Physiol Behav (2014), http://dx.(psychological), 20 min forced swim (physical) and ether anesthesia 77 (endocrinological), respectively. Application of these stresses increases 78 serum corticosterone levels, and by combining three different kinds of 79 stresses, the SPS model could accomplish severity of symptoms analo-80 gous to that of PTSD [10,11]. Studies have shown that rats that undergo 81 the SPS procedure suffer from increased anxiety and impairment of 82 social and object recognition memory [12] and present with changes 83 in glucocorticoid and mineralocorticoid receptors involved in the 84 HPA system [13,14]. Extensive evidence shows that regular exercise 85 is beneficial in ameliorating memory impairment, enhancing cogni-86 tive function and preventing memory decline [15,16]. Therefore, 87 exercise may be beneficial in reversing PTSD-induced symptoms in-88 cluding anxiety and depressive behaviors and learning and memory 89 function impairment [17]. Statistics show that individuals who suffer 90 from PTSD tend, on an average, to exercise less (including activities 91 such as shopping, walking, and sports) compared to before the onset 92 of the disorder [18,19]. Patients also reported poor compliance to 93 medication [19]. 94 In the present study we used the SPS rat model of PTSD to study the 95 effect of regular exercise as a potential non-pharmacological therapeu-96 tic approach for attenuating SPS-induced deficits including anxiety-97 like (anxiety), depression-like (depression) behaviors, and learning 98 and memory function impairment. 99 2. Materials and methods 100 2.1. Animals 101 Male Wistar rats (175-200 g; Charles River, Wilmington, MA) were 102 housed with a 12-h light, 12-h dark cycle (lights on at 0600 h) in a 103 climate-controlled room with ad libitum food and water. After arrival 104 at the research facility, all rats were allowed 1 week to acclimate before 105 manipulations began (Scheme 1). All experiments were conducted in 106 accordance with the NIH guidelines using approved protocols from 107 the University of Houston Animal Care Committee. 108 2.2. Single-prolonged stress model 109 Male Wistar rats were assigned into 4 groups; group 1: control, 110 group 2: SPS, group 3: exercised, group 4: SPS-exercised. 111 Single prolonged stress (SPS): The two SPS groups: SPS and exercise 112 SPS rats (10 rats/group) were subjected to a one time combined stress 113 paradigm applied consecutively in a day [9,20]: immobilization 114 (compression with double layered plastic Ziploc bag with edges cov-115 ered in duct tape to prevent the rats from escaping and also an open-116 ing for the rat nose was provided in the Ziploc bag) for 2 h followed 117 immediately by 20 min of forced swimming (in a tall cylindrical tank 118
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