Effects of adolescent alcohol exposure on stress-induced reward deficits,
brain CRF, monoamines and glutamate in adult rats
James P. Kesby
Received: 1 May 2017 /Accepted: 13 November 2017 /Published online: 27 November 2017
Springer-Verlag GmbH Germany, part of Springer Nature 2017
Background Adolescent alcohol exposure may increase depression vulnerability in adulthood by increasing the anhedonic
response to stress.
Methods Male Wistar rats (postnatal days 28–53) were exposed to binge-like adolescent intermittent ethanol (AIE) or water. In
adulthood, rats were exposed to social defeat, consisting of daily confrontations with an aggressive conspecific, followed by
testing of brain reward function in a discrete-trial current-intensity intracranial self-stimulation procedure for 10 consecutive days.
Neurochemistry and corticotropin-releasing factor (CRF) and CRF receptor 1 (CRFR1) mRNA levels were assessed in
corticolimbic brain areas on day 11 of social defeat stress.
Results Social defeat elevated reward thresholds in both AIE- and water-exposed rats indicating stress-induced anhedonia.
However, AIE-exposed rats were more likely to show threshold elevations after repeated stress compared to water-exposed rats.
AIE exposure decreased CRF mRNA levels in the nucleus accumbens and increased CRFR1 mRNA levels in the prefrontal
cortex, while stress increased CRF mRNA levels in the central amygdala. In the caudate putamen, AIE exposure decreased
dopamine turnover, while stress increased glutamate and serotonin metabolism and turnover.
Conclusions These results demonstrate increased risk of repeated stress-induced anhedonia after AIE exposure, an effect that may
be due to alterations in brain CRF and dopamine systems. These results suggest that the increased rates of depression reported in
people with a history of adolescent alcohol exposure may be related to alterations in brain reward and stress systems that may
contribute to increased stress-induced anhedonia.
The high prevalence of alcohol binge drinking at very high
intoxication levels among adolescents is an important public
health concern (Johnston et al. 2014; Schuckit et al. 2014;
Windle et al. 2008). Ethanol consumption at neurotoxic doses
during adolescence causes damage to frontal cortical brain
areas undergoing maturation (Bava and Tapert 2010;
Jacobus and Tapert 2013;Squegliaetal.2014). Considering
that corticolimbic brain areas mediate reward processing and
depression (Koob and Volkow 2010; Russo and Nestler
2013), underage drinking may lead to altered responses to
reward (Migliorini et al. 2013) and an increased risk of major
depression (Boden and Fergusson 2011; Briere et al. 2014)
later in life. A few longitudinal studies have found causal links
between heavy ethanol use during adolescence and the onset
of depressive symptoms (Fergusson et al. 2009), as well as
Nathalie Boutros and Andre Der-Avakian are first co-authors
Athina Markou and Svetlana Semenova are senior co-authors
Electronic supplementary material The online version of this article
(https://doi.org/10.1007/s00213-017-4789-0) contains supplementary
material, which is available to authorized users.
* Svetlana Semenova
University of California San Diego, La Jolla, CA, USA
Queensland Brain Institute, The University of Queensland, St.
Lucia, Queensland, Australia
The Clayton Foundation Laboratories for Peptide Biology, The Salk
Institute for Biological Studies, La Jolla, CA 92037, USA
Present address: PAREXEL International, 1560 E Chevy Chase Dr,
Glendale, CA 91206, USA
Psychopharmacology (2018) 235:737–747