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Neuroscience. 2019 Aug 23;418:133-148. doi: 10.1016/j.neuroscience.2019.08.030. [Epub ahead of print]

Increased Ethanol Consumption and Locomotion Develop upon Ethanol Deprivation in Rats Overexpressing the Adenosine (A)2A Receptor.

Author information

1
Maj Institute of Pharmacology, Polish Academy of Sciences, Department of Drug Addiction Pharmacology, 31-343 Kraków, 12 Smętna street, Poland; Maj Institute of Pharmacology, Polish Academy of Sciences, Department of Pharmacology, Laboratory of Pharmacology and Brain Biostructure, 31-343 Kraków, 12 Smętna street, Poland. Electronic address: zaniew@if-pan.krakow.pl.
2
Maj Institute of Pharmacology, Polish Academy of Sciences, Department of Drug Addiction Pharmacology, 31-343 Kraków, 12 Smętna street, Poland.
3
Department of Forensic Medicine, Faculty of Medicine, Jagiellonian University Medical College, Grzegórzecka 16 St., 31-531 Kraków, Poland.
4
Max-Delbrück-Center for Molecular Medicine, Department of Cardiovascular Research, Molecular Biology of Peptide Hormones, Robert-Rössle-Str. 10, 13125 Berlin, Germany; Berlin Institute of Health (BIH), Anna-Louisa-Karsch-Straße 2, 10178 Berlin, Germany; Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany; DZHK (German Centre for Cardiovascular Research; Deutsches Zentrum für Herz-Kreislauf-Forschung), Partner Site Berlin, Hessische Strasse 3-4, 10115 Berlin, Germany; Institute for Biology, University of Lübeck, Ratzeburger Allee 160, 23562 Lübeck, Germany.
5
Department of Neuroscience, Karolinska Institute, Retzius väg 8, 171 77 Stockholm, Sweden.

Abstract

Preclinical data indicate that ethanol produces behavioral effects that can be regulated by many neurotransmitters and neuromodulators like adenosine (A). The most important receptors with respect to the rewarding effects of ethanol seem to be the A2A receptors. This study used a transgenic strategy, specifically rats overexpressing the A2A receptor, to characterize the neurobiological mechanisms of ethanol consumption as measured by intermittent access to 20% ethanol in a two-bottle choice paradigm. In this model, no change in ethanol consumption was observed in transgenic animals compared to wild type controls during the acquisition/maintenance phase. Following alcohol deprivation, only transgenic rats overexpressing the A2A receptor exhibited escalation of ethanol consumption and drank more (by ca. 90%), but not significantly, ethanol than did the wild type rats. During ethanol withdrawal, the immobility time of rats overexpressing the A2A receptor in the forced swim test was lower than that of wild type rats. Moreover, transgenic rats withdrawn from ethanol, compared to the drug-naive transgenic animals, exhibited an increase above 70% in locomotion. The results indicated that the overexpression of A2A receptors may be a risk factor for the escalation of ethanol consumption despite the reduction in depression-like signs of ethanol withdrawal.

KEYWORDS:

A(2A) receptor overexpression; a two-bottle choice test; forced swim test; intermittent access to alcohol; locomotor activity

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