D. Maysinger

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The research of my laboratory encompasses studies of neural cell interactions under physiological and pathological conditions, roles of organelles in such conditions, and the impact of nanostructures on neural cells.

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SMAN 1 Kota Serang

Lourdes Astrid de la Torre

Zofia Rosińska

Selena Bartlett

Andries Kalsbeek

Academic Medical Centre/ Universiteit van Amsterdam

Esi Domi

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Differential Effects of Acute and Chronic Ethanol Exposure on Orexin Expression in the Perifornical Lateral Hypothalamus

Alcoholism: Clinical and Experimental Research, 2010

Background-Recent reports support the involvement of hypothalamic orexigenic peptides in stimulat... more Background-Recent reports support the involvement of hypothalamic orexigenic peptides in stimulating ethanol intake. Our previous studies have examined the effects of ethanol on hypothalamic peptide systems of the paraventricular nucleus of the hypothalamus (PVN) and identified a positive feedback loop in which PVN peptides, such as enkephalin and galanin, stimulate ethanol intake and ethanol, in turn, stimulates the expression of these peptides. Recently, orexin (OX), a peptide produced mainly by cells in the perifornical lateral hypothalamus (PFLH), has been shown to play an important role in mediating the rewarding aspects of ethanol intake. However, there is little evidence showing the effects that ethanol itself may have on the OX peptide system. In order to understand the feedback relationship between ethanol and the OX system, the current investigation was designed to measure OX gene expression in the PFLH following acute as well as chronic ethanol intake. Methods-In the first experiment, Sprague-Dawley rats were trained to voluntarily consume a 2% or 9% concentration of ethanol, and the expression of OX mRNA in the PFLH was measured using quantitative real-time polymerase chain reaction (qRT-PCR). The second set of experiments tested the impact of acute oral gavage of 0.75 and 2.5 g/kg ethanol solution on OX expression in the PFLH using qRT-PCR, as well as radiolabeled in situ hybridization. Further tests using digoxigenin-labeled in situ hybridization and immunofluorescence histochemistry allowed us to more clearly distinguish the effects of acute ethanol on OX cells in the lateral hypothalamic (LH) vs perifornical (PF) regions. Results-The results showed chronic consumption of ethanol vs water to dose-dependently reduce OX mRNA in the PFLH, with a larger effect observed in rats consuming 2.5 g/kg/day (-70%) or 1.0 g/kg/day (-50%) compared to animals consuming 0.75 g/kg/day (-40%). In contrast to chronic intake, acute oral ethanol compared to water significantly enhanced OX expression in the PFLH, and this effect occurred at the lower (0.75 g/kg) but not higher (2.5 g/kg) dose of ethanol. Additional analyses of the OX cells in the LH vs PF regions identified the former as the primary site of ethanol's stimulatory effect on the OX system. In the LH but not the PF, acute ethanol increased the density of OX-expressing and OX-immunoreactive neurons. The increase in

D. Maysinger

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