Voluntary and forced exposure to ethanol vapor produces similar escalation of alcohol drinking but differential recruitment of brain regions related to stress, habit, and reward in male rats

Giordano de Guglielmo, Sierra Simpson, Adam Kimbrough, Dana Conlisk, Robert Baker, Maxwell Cantor, Marsida Kallupi, Olivier George
Neuropharmacology. 2023-01-01; 222: 109309
DOI: 10.1016/j.neuropharm.2022.109309

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de Guglielmo G(1), Simpson S(2), Kimbrough A(3), Conlisk D(4), Baker R(2), Cantor M(2), Kallupi M(2), George O(2).

Author information:
(1)Department of Psychiatry, University of California San Diego, La Jolla, CA,
USA. Electronic address: .
(2)Department of Psychiatry, University of California San Diego, La Jolla, CA,
(3)Department of Basic Medical Sciences, College of Veterinary Medicine, Purdue
University, West Lafayette, IN, 47906, USA.
(4)Univ. Bordeaux, INSERM, Neurocenter Magendie, Psychobiology of Drug Addiction
Group, U1215, F-33000, Bordeaux, France.

A major limitation of the most widely used current animal models of alcohol
dependence is that they use forced exposure to ethanol including
ethanol-containing liquid diet and chronic intermittent ethanol (CIE) vapor to
produce clinically relevant blood alcohol levels (BAL) and addiction-like
behaviors. We recently developed a novel animal model of voluntary induction of
alcohol dependence using ethanol vapor self-administration (EVSA). However, it
is unknown whether EVSA leads to an escalation of alcohol drinking per se, and
whether such escalation is associated with neuroadaptations in brain regions
related to stress, reward, and habit. To address these issues, we compared the
levels of alcohol drinking during withdrawal between rats passively exposed to
alcohol (CIE) or voluntarily exposed to EVSA and measured the number of
Fos+ neurons during acute withdrawal (16 h) in key brain regions important for
stress, reward, and habit-related processes. CIE and EVSA rats exhibited similar
BAL and similar escalation of alcohol drinking and motivation for alcohol during
withdrawal. Acute withdrawal from EVSA and CIE recruited a similar number of
Fos+ neurons in the Central Amygdala (CeA), however, acute withdrawal from EVSA
recruited a higher number of Fos+ neurons in every other brain region analyzed
compared to acute withdrawal from CIE. In summary, while the behavioral measures
of alcohol dependence between the voluntary (EVSA) and passive (CIE) model were
similar, the recruitment of neuronal ensembles during acute withdrawal was very
different. The EVSA model may be particularly useful to unveil the neuronal
networks and pharmacology responsible for the voluntary induction and
maintenance of alcohol dependence and may improve translational studies by
providing preclinical researchers with an animal model that highlights the
volitional aspects of alcohol use disorder.

Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.


Auteurs Bordeaux Neurocampus