Joseph Porter

Virginia Commonwealth University, Psychology, Department Member

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Address: Richmond, Virginia, United States

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University of Oviedo / Universidad de Oviedo

Emis Akbari

George Brown College

R. Fitch

University of Connecticut

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Norwegian University of Life Sciences

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Papers by Joseph Porter

Erratum to: Schedule-induced and water-deprivation-induced drinking in rats: Effects of hypertonic saline challenges to homeostatic thirst mechanisms

Bulletin of the psychonomic society, Jun 1, 1983

Organizing action of prenatally administered testosterone propionate on the tissues mediating mat... more

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Failure to block opiate effects of oral etonitazene with naltrexone during 24-h choice testing

Bulletin of the psychonomic society, Mar 1, 1985

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Reply to: Rapid antidepressant effects and abuse liability of ketamine

Psychopharmacology, Mar 23, 2014

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Haloperidol blocks reacquisition of operant running during extinction following a single priming trial with food reward

Bulletin of the psychonomic society, Apr 1, 1989

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Compound stimulus control of operant, but not adjunctive, behavior

Bulletin of the psychonomic society, Sep 1, 1978

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Route of administration influences substitution patterns in rats trained to discriminate methadone vs. vehicle

Drug and Alcohol Dependence, Aug 1, 2009

Replacement therapy with the synthetic μ-opioid agonist methadone is an efficacious treatment for... more Replacement therapy with the synthetic μ-opioid agonist methadone is an efficacious treatment for opioid abuse. While much is known about methadone's pharmacology, its discriminative stimulus properties remain largely unexplored. The present study sought to establish methadone discrimination in rats. Moreover, some research suggests that route of administration alters the discriminative stimulus of methadone. Thus, the present study also compared intraperitoneal (i.p.) and subcutaneous (s.c.) routes of administration. Male Sprague-Dawley rats were trained to discriminate 3.0 mg/kg methadone (i.p.) from vehicle in a two-lever discrimination procedure. Generalization tests were conducted with a variety of compounds administered i.p. and s.c. Methadone fully substituted for itself, yielding ED 50 s of 1.5 mg/kg (i.p.) and 0.2 mg/kg (s.c.). Naltrexone (i.p.), an opioid antagonist produced a dose-dependent reduction in methadoneappropriate responding. The methadone stereoisomers fully substituted for methadone when given s.c.; however, when administered i.p., (+) and (-) methadone produced partial and no substitution, respectively. Heroin fully generalized to methadone regardless of administration route, while morphine fully substituted when given s.c., but not i.p. The kappa-agonist U50-488 failed to generalize to methadone with either route of administration. These results demonstrated that methadone's discriminative stimulus is mediated through μ-opioid receptor activity and is similar to that of commonly abused opioids (heroin, morphine). Additionally, route of administration produced differential results for many of the drugs tested, suggesting decreased drug bioavailability following i.p. administration due to hepatic first pass metabolism. Taken together, these results suggest that methadone's shared subjective effects with abused opioids, as well as its unique metabolic properties contribute to its efficacy in opioid maintenance therapy.

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Effects of (2R,6R)-hydroxynorketamine in assays of acute pain-stimulated and pain-depressed behaviors in mice

PloS one, Apr 19, 2024

Ketamine has been shown to produce analgesia in various acute and chronic pain states; however, a... more Ketamine has been shown to produce analgesia in various acute and chronic pain states; however, abuse liability concerns have limited its utility. The ketamine metabolite (2R,6R)hydroxynorketamine (HNK) has been shown to produce antidepressant-like effects similar to ketamine without abuse liability concerns. (2R,6R)-HNK produces sustained analgesia in models of chronic pain, but has yet to be evaluated in models of acute pain. The present study evaluated the efficacy of acute (2R,6R)-HNK administration (one injection) in assays of pain-stimulated (52-and 56-degree hot plate test and acetic acid writhing) and paindepressed behavior (locomotor activity and rearing) in male and female C57BL/6 mice. In assays of pain-stimulated behaviors, (2R,6R)-HNK (1-32 mg/kg) failed to produce antinociception in the 52-and 56-degree hot plate and acetic acid writhing assays. In assays of pain-depressed behaviors, 0.56% acetic acid produced a robust depression of locomotor activity and rearing that was not blocked by pretreatment of (2R,6R)-HNK (3.2-32 mg/kg). The positive controls morphine (hot plate test) and ketoprofen (acetic acid writhing, locomotor activity, and rearing) blocked pain-stimulated and pain-depressed behaviors. Finally, the effects of intermittent (2R,6R)-HNK administration were evaluated in 52-degree hot plate and pain-depressed locomotor activity and rearing. Intermittent administration of (2R,6R)-HNK also did not produce antinociceptive effects in the hot plate or pain-depressed locomotor activity assays. These results suggest that (2R,6R)-HNK is unlikely to have efficacy in treating acute pain; however, the efficacy of (2R,6R)-HNK in chronic pain states should continue to be evaluated.

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How to account for hallucinations in the interpretation of the antidepressant effects of psychedelics: a translational framework

Psychopharmacology

Rationale Recent trials with psychedelics in major depressive disorder and treatment-resistant de... more Rationale Recent trials with psychedelics in major depressive disorder and treatment-resistant depression showed remarkable improvements in depressive symptoms that can last for up to several months after even a single administration. The lack of an appropriate placebo control group—as patients are often able to discriminate the subjective effects of the drug—and an incomplete understanding of the role of the hallucinogenic and mystical experience, hampers the interpretation of these therapeutic effects. Objectives To control for these factors, we developed a translational framework based on establishing pharmacokinetic/pharmacodynamic (PK/PD) relationships in rodents and humans for hallucinogenic (i.e., discriminative stimulus effects in rodents and humans; head twitch responses in rodents; questionnaires in humans) and therapeutic effects. For the latter, we selected the pattern separation and attentional set-shifting tasks as measures for cognitive flexibility because of their hi...

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Differential effects of dopamine blockers on the acquisition of schedule-induced drinking and deprivation-induced drinking

Physiological Psychology, 1984

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Antipsychotic drugs: comparison in animal models of efficacy, neurotransmitter regulation, and neuroprotection

Pharmacological reviews, 2008

Various lines of evidence indicate the presence of progressive pathophysiological processes occur... more Various lines of evidence indicate the presence of progressive pathophysiological processes occurring within the brains of patients with schizophrenia. By modulating chemical neurotransmission, antipsychotic drugs may influence a variety of functions regulating neuronal resilience and viability and have the potential for neuroprotection. This article reviews the current literature describing preclinical and clinical studies that evaluate the efficacy of antipsychotic drugs, their mechanism of action and the potential of first- and second-generation antipsychotic drugs to exert effects on cellular processes that may be neuroprotective in schizophrenia. The evidence to date suggests that although all antipsychotic drugs have the ability to reduce psychotic symptoms via D(2) receptor antagonism, some antipsychotics may differ in other pharmacological properties and their capacities to mitigate and possibly reverse cellular processes that may underlie the pathophysiology of schizophrenia.

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Route of administration influences substitution patterns in rats trained to discriminate methadone vs. vehicle

Drug and Alcohol Dependence, 2009

Replacement therapy with the synthetic μ-opioid agonist methadone is an efficacious treatment for... more Replacement therapy with the synthetic μ-opioid agonist methadone is an efficacious treatment for opioid abuse. While much is known about methadone's pharmacology, its discriminative stimulus properties remain largely unexplored. The present study sought to establish methadone discrimination in rats. Moreover, some research suggests that route of administration alters the discriminative stimulus of methadone. Thus, the present study also compared intraperitoneal (i.p.) and subcutaneous (s.c.) routes of administration. Male Sprague-Dawley rats were trained to discriminate 3.0 mg/kg methadone (i.p.) from vehicle in a two-lever discrimination procedure. Generalization tests were conducted with a variety of compounds administered i.p. and s.c. Methadone fully substituted for itself, yielding ED 50 s of 1.5 mg/kg (i.p.) and 0.2 mg/kg (s.c.). Naltrexone (i.p.), an opioid antagonist produced a dose-dependent reduction in methadoneappropriate responding. The methadone stereoisomers fully substituted for methadone when given s.c.; however, when administered i.p., (+) and (−) methadone produced partial and no substitution, respectively. Heroin fully generalized to methadone regardless of administration route, while morphine fully substituted when given s.c., but not i.p. The kappa-agonist U50-488 failed to generalize to methadone with either route of administration. These results demonstrated that methadone's discriminative stimulus is mediated through μ-opioid receptor activity and is similar to that of commonly abused opioids (heroin, morphine). Additionally, route of administration produced differential results for many of the drugs tested, suggesting decreased drug bioavailability following i.p. administration due to hepatic first pass metabolism. Taken together, these results suggest that methadone's shared subjective effects with abused opioids, as well as its unique metabolic properties contribute to its efficacy in opioid maintenance therapy.

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Schedule-induced and water-deprivation-induced drinking in rats: Effects of hypertonic saline challenges to homeostatic thirst mechanisms

Bulletin of the Psychonomic Society, 1983

APA PsycNET Our Apologies! - The following features are not available with your current Browser c... more

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Vortioxetine Differentially Modulates MK-801-Induced Changes in Visual Signal Detection Task Performance and Locomotor Activity

Frontiers in pharmacology, 2018

Attention impairment is a common feature of Major Depressive Disorder (MDD), and MDD-associated c... more Attention impairment is a common feature of Major Depressive Disorder (MDD), and MDD-associated cognitive dysfunction may play an important role in determining functional status among this patient population. Vortioxetine is a multimodal antidepressant that may improve some aspects of cognitive function in MDD patients, and may indirectly increase glutamate neurotransmission in brain regions classically associated with attention function. Previous non-clinical research suggests that vortioxetine has limited effects on attention. This laboratory previously found that vortioxetine did not improve attention function in animals impaired by acute scopolamine administration, using the visual signal detection task (VSDT). However, vortioxetine has limited effects on acetylcholinergic neurotransmission, and thus it is possible that attention impaired by other mechanisms would be attenuated by vortioxetine. This study sought to investigate whether acute vortioxetine administration can attenu...

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Effects of body weight and level of deprivation on activity of rats with lesions of the ventromedial hypothalamus

Physiological Psychology

Nine VMH-Iesioned rats were tested for photocell and open-field activity at nonobese and obese bo... more Nine VMH-Iesioned rats were tested for photocell and open-field activity at nonobese and obese body weights at 0%, 10%, and 20% deprivation. An increased activity level was displayed by the nonobese VMH animals, but only under food-deprivation conditions. Conversely, a decreased activity level was displayed by obese VMH animals, but once again, only during deprived testing conditions. The results are discussed in terms of recent findings regarding the VMH•lesioned rat's activity level and willingness to work for food. The term "ventromedial hypothalamus" (VMH) is used to describe that portion of the hypothalamus which, when lesioned, produces hyperphagia. The hyperphagia is accompanied by a very rapid weight gain, often resulting in a doubling of the animal's original body weight (Brobeck, Tepperman, & Long, 1943; Hetherington & Ranson, 1940). The VMH includes, but is not limited to, the VM nuclei. This distinction is important, since recent work (Gold, 1973) has questioned the role of the VM nuclei in hypothalamic hyperphagia. One might predict that an animal which overeats (as a result of VMH lesions) would also demonstrate an increased motivation on food-directed (barpressing) tasks, but this has yet to be convincingly demonstrated. It has been shown that rats with VMH lesions display a decrease in motivation (e.g., Miller, Bailey, & Stevenson, 1950; Teitelbaum, 1957), an increase in motivation (e.g., Falk, 1961; Kent & Peters, 1973), or no change in motivation (e.g., Porter & Allen, 1972; Sclafani, 1971). Several variables have been mentioned by various investigators (e.g., Marks & Remley, 1972; Porter & Allen, 1977; Sclafani, 1976; Singh, 1970) to clarify these discrepant results. These factors include the body weight of the VMHlesioned rat at the time of testing, the amount of preoperative or postoperative training, and the level of deprivation at the time of testing. Marks and Remley (1972), Porter, Allen, and Arazie (1974), and Wampler (1973) have reported that at nonobese weight levels the performance of VMH-Iesioned rats is similar to or higher than that of normal rats, but at obese weight levels they typi-This stud y was based upon a thesis submitted by the senior author in partial fulfillment of the requirrnent s for the Master of Science degree in Psychology at Virginia Commonwealth University. Reprint requests should be sent to

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Failure to block opiate effects of oral etonitazene with naltrexone during 24-h choice testing

Bulletin of the Psychonomic Society

Thirty rats were given access to 5-pg/ml etonitazene and D.l-mg/ml quinine solutions during 12 da... more Thirty rats were given access to 5-pg/ml etonitazene and D.l-mg/ml quinine solutions during 12 days of 24-hchoicetestingwith a single daily 3-mg/kgnaltrexone injection (Group N-CT),two 3-mg/kgnaltrexone injections per day (Group 2N-CT),or a single daily vehicle (l-ml/kg saline) injection (Group Sal-CT). Control groups received either the daily naltrexone treatment or saline, and were provided with only water. Both naltrexone groups receiving choice tests displayed signs ofprecipitated withdrawal upon naltrexone administration.When drugsolutions were replaced with water and intraperitoneal injections were terminated, spontaneous withdrawal was displayed by all three choice test groups. The results clearly demonstrate that naltrexone does not block the pharamacological properties ofetonitazene in a 24-h choice test paradigm. Thus, procedures for separating taste factors from pharmacological properties of etonitazene with choice testing must employ limited access to the opiate. One of the problems in studying oral intake of opiate drugs is that of palatability. Although animals will readily self-administer opiates via other routes, such as intravenously (Deneau, Yanagita, & Seevers, 1969; Woods & Schuster, 1968), the bitter taste of these alkaloids in solution makes it difficult to study their pharmacological properties with oral self-administration paradigms. One approach for separating taste factors and pharmacological properties is to provide an equally bitter placebo solution (such as quinine) in choice testing with the opiate solution. Chipkin and Rosecrans (1978) and Lynch, Porter, and Rosecrans (1984) have shown that the bitter taste of methadone can be taste-balanced with a quinine solution during 24-h choice testing. In these studies, solutions were determined to be equally palatable when chosen 50% of the time by rats given daily injections of naltrexone (3 mg/kg), a long-acting narcotic antagonist

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Discriminative stimulus properties of 1.25 mg/kg clozapine in rats: mediation by serotonin 5-HT2and dopamine D4 receptors

Brain research, Oct 5, 2016

The atypical antipsychotic drug clozapine remains one of most effective treatments for schizophre... more The atypical antipsychotic drug clozapine remains one of most effective treatments for schizophrenia, given a lack of extrapyramidal side effects, improvements in negative symptoms, cognitive impairment, and in symptoms in treatment-resistant schizophrenia. The adverse effects of clozapine, including agranulocytosis, make finding a safe clozapine-like a drug a goal for drug developers. The drug discrimination paradigm is a model of interoceptive stimulus that has been used in an effort to screen experimental drugs for clozapine-like atypical antipsychotic effects. The present study was conducted to elucidate the receptor-mediated stimulus properties that form this clozapine discriminative cue by testing selective receptor ligands in rats trained to discriminate a 1.25mg/kg dose of clozapine from vehicle in a two choice drug discrimination task. Full substitution occurred with the 5-HT2A inverse agonist M100907 and the two preferential D4/ 5-HT2/ α1 receptor antagonists Lu 37-114 ((S...

Assessment of drug discrimination as a preclinical assay for development of antipsychotic drugs

F1000posters, May 10, 2011

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The Discriminative Stimulus Properties of Drugs Used to Treat Depression and Anxiety

Current Topics in Behavioral Neurosciences, 2016

Drug discrimination is a powerful tool for evaluating the stimulus effects of psychoactive drugs ... more Drug discrimination is a powerful tool for evaluating the stimulus effects of psychoactive drugs and for linking these effects to pharmacological mechanisms. This chapter reviews the primary findings from drug discrimination studies of antidepressant and anxiolytic drugs, including novel pharmacological mechanisms. The stimulus properties revealed from these animal studies largely correspond to the receptor affinities of antidepressant and anxiolytic drugs, indicating that subjective effects may correspond to either therapeutic or side effects of these medications. We discuss drug discrimination findings concerning adjunctive medications and novel pharmacologic strategies in antidepressant and anxiolytic research. Future directions for drug discrimination work include an urgent need to explore the subjective effects of medications in animal models, to better understand shifts in stimulus sensitivity during prolonged treatments, and to further characterize stimulus effects in female subjects. We conclude that drug discrimination is an informative preclinical procedure that reveals the interoceptive effects of pharmacological mechanisms as they relate to behaviors that are not captured in other preclinical models.

Differential tolerance to the behavioral effects of chronic pimozide and clozapine on multiple random interval responding in rats

Behav Pharmacol, 1993

The behavioral effects of 10 days of chronic administration of the typical neuroleptic, pimozide,... more The behavioral effects of 10 days of chronic administration of the typical neuroleptic, pimozide, and the atypical neuroleptic, clozapine, were compared on a schedule of multiple random interval responding for food reinforcement and on photocell activity in rats. The low doses of both neuroleptics (0.125mg/kg pimozide, 1.25mg/kg clozapine) had little effect on any of the dependent variables measured. The high doses (1.0mg/kg pimozide, 10.0mg/kg clozapine) significantly disrupted response rates and reinforcement rates and significantly increased response duration when the drugs were first administered. Chronic administration, however, resulted in different profiles for the two drugs. While tolerance developed to the disruptive effects of clozapine, tolerance did not develop to the disruptive effects of pimozide and, on some dependent measures, an increased sensitivity developed. No tolerance developed to the disruptive effects of either drug on photocell activity. The effects of the drugs depended on the reinforcement density of the operant schedule.

Task- and treatment length-dependent effects of vortioxetine on scopolamine-induced cognitive dysfunction and hippocampal extracellular acetylcholine in rats

Journal of Pharmacology and Experimental Therapeutics, 2016

Major depressive disorder (MDD) is a common psychiatric disorder that often features impairments ... more Major depressive disorder (MDD) is a common psychiatric disorder that often features impairments in cognitive function, and these cognitive symptoms can be important determinants of functional ability. Vortioxetine is a multimodal antidepressant that may improve some aspects of cognitive function in patients with MDD, including attention, processing speed, executive function, and memory. However, the cause of these effects is unclear, and there are several competing theories on the underlying mechanism, notably including regionally-selective downstream enhancement of glutamate neurotransmission and increased acetylcholine (ACh) neurotransmission. The current work sought to evaluate the ACh hypothesis by examining vortioxetine's ability to reverse scopolamine-induced impairments in rodent tests of memory and attention. Additionally, vortioxetine's effects on hippocampal extracellular ACh levels were examined alongside studies of vortioxetine's pharmacokinetic profile. We found that acute vortioxetine reversed scopolamine-induced impairments in social and object recognition memory, but did not alter scopolamine-induced impairments in attention. Acute vortioxetine also induced a modest and short-lived increase in hippocampal ACh levels. However, this short-term effect is at variance with vortioxetine's moderately long brain half life (5.1 hours). Interestingly, subchronic vortioxetine treatment failed to reverse scopolamine-induced social recognition memory deficits and had no effects on basal hippocampal ACh levels. These data suggest that vortioxetine has some effects on memory that could be mediated through cholinergic neurotransmission, however these effects are modest and only seen under acute dosing conditions. These limitations may argue against cholinergic mechanisms being the primary mediator of vortioxetine9s cognitive effects, which are observed under chronic dosing conditions in patients with MDD.

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Erratum to: Schedule-induced and water-deprivation-induced drinking in rats: Effects of hypertonic saline challenges to homeostatic thirst mechanisms

Bulletin of the psychonomic society, Jun 1, 1983

Organizing action of prenatally administered testosterone propionate on the tissues mediating mat... more

Download

Failure to block opiate effects of oral etonitazene with naltrexone during 24-h choice testing

Bulletin of the psychonomic society, Mar 1, 1985

Download

Reply to: Rapid antidepressant effects and abuse liability of ketamine

Psychopharmacology, Mar 23, 2014

Download

Haloperidol blocks reacquisition of operant running during extinction following a single priming trial with food reward

Bulletin of the psychonomic society, Apr 1, 1989

Download

Compound stimulus control of operant, but not adjunctive, behavior

Bulletin of the psychonomic society, Sep 1, 1978

Download

Route of administration influences substitution patterns in rats trained to discriminate methadone vs. vehicle

Drug and Alcohol Dependence, Aug 1, 2009

Download

Effects of (2R,6R)-hydroxynorketamine in assays of acute pain-stimulated and pain-depressed behaviors in mice

PloS one, Apr 19, 2024

Download

How to account for hallucinations in the interpretation of the antidepressant effects of psychedelics: a translational framework

Psychopharmacology

Download

Differential effects of dopamine blockers on the acquisition of schedule-induced drinking and deprivation-induced drinking

Physiological Psychology, 1984

Download

Antipsychotic drugs: comparison in animal models of efficacy, neurotransmitter regulation, and neuroprotection

Pharmacological reviews, 2008

Download

Route of administration influences substitution patterns in rats trained to discriminate methadone vs. vehicle

Drug and Alcohol Dependence, 2009

Replacement therapy with the synthetic μ-opioid agonist methadone is an efficacious treatment for... more Replacement therapy with the synthetic μ-opioid agonist methadone is an efficacious treatment for opioid abuse. While much is known about methadone's pharmacology, its discriminative stimulus properties remain largely unexplored. The present study sought to establish methadone discrimination in rats. Moreover, some research suggests that route of administration alters the discriminative stimulus of methadone. Thus, the present study also compared intraperitoneal (i.p.) and subcutaneous (s.c.) routes of administration. Male Sprague-Dawley rats were trained to discriminate 3.0 mg/kg methadone (i.p.) from vehicle in a two-lever discrimination procedure. Generalization tests were conducted with a variety of compounds administered i.p. and s.c. Methadone fully substituted for itself, yielding ED 50 s of 1.5 mg/kg (i.p.) and 0.2 mg/kg (s.c.). Naltrexone (i.p.), an opioid antagonist produced a dose-dependent reduction in methadoneappropriate responding. The methadone stereoisomers fully substituted for methadone when given s.c.; however, when administered i.p., (+) and (−) methadone produced partial and no substitution, respectively. Heroin fully generalized to methadone regardless of administration route, while morphine fully substituted when given s.c., but not i.p. The kappa-agonist U50-488 failed to generalize to methadone with either route of administration. These results demonstrated that methadone's discriminative stimulus is mediated through μ-opioid receptor activity and is similar to that of commonly abused opioids (heroin, morphine). Additionally, route of administration produced differential results for many of the drugs tested, suggesting decreased drug bioavailability following i.p. administration due to hepatic first pass metabolism. Taken together, these results suggest that methadone's shared subjective effects with abused opioids, as well as its unique metabolic properties contribute to its efficacy in opioid maintenance therapy.

Download

Schedule-induced and water-deprivation-induced drinking in rats: Effects of hypertonic saline challenges to homeostatic thirst mechanisms

Bulletin of the Psychonomic Society, 1983

APA PsycNET Our Apologies! - The following features are not available with your current Browser c... more

Download

Vortioxetine Differentially Modulates MK-801-Induced Changes in Visual Signal Detection Task Performance and Locomotor Activity

Frontiers in pharmacology, 2018

Download

Effects of body weight and level of deprivation on activity of rats with lesions of the ventromedial hypothalamus

Physiological Psychology

Download

Failure to block opiate effects of oral etonitazene with naltrexone during 24-h choice testing