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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Environmental enrichment enhances conditioned place preference to ethanol via an oxytocinergic-dependent mechanism in male mice

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Rae, Mariana [1, 2] ; Zanos, Panos [1, 3] ; Georgiou, Polymnia [1, 3] ; Chivers, Priti [1] ; Bailey, Alexis [1, 4] ; Camarini, Rosana [2]
Total Authors: 6
[1] Univ Surrey, Fac Hlth & Med Sci, Guildford, Surrey - England
[2] Univ Sao Paulo, Dept Farmacol, BR-05508900 Sao Paulo, SP - Brazil
[3] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 - USA
[4] St Georges Univ London, Inst Med & Biomed Educ, London - England
Total Affiliations: 4
Document type: Journal article
Source: Neuropharmacology; v. 138, p. 267-274, AUG 2018.
Web of Science Citations: 7

Environmental conditions, such as stress and environmental enrichment (EE), influence predisposition to alcohol use/abuse; however, the underlying mechanisms remain unknown. To assess the effect of environmental conditions on the initial rewarding effects of alcohol, we examined conditioned place-preference (CPP) to alcohol following exposure to EE in mice. Since social context is a major factor contributing to initial alcohol-drinking, we also assessed the impact of EE on the levels of the ``social neuropeptide{''} oxytocin (OT) and its receptor, OTR. Finally, we assessed the effect of pharmacological manipulations of the oxytocinergic system on EE-induced alcohol CPP. While EE increased sociability and reduced anxiety-like behaviors, it caused a similar to 3.5-fold increase in alcohol reward compared to controls. EE triggered profound neuroadaptations of the oxytocinergic system; it increased hypothalamic OT levels and decreased OTR binding in the prefrontal cortex and olfactory nuclei of the brain. Repeated administration of the OT analogue carbetocin (6.4 mg/kg/day) mimicked the behavioral effects of EE on ethanol CPP and induced similar brain region-specific alterations of OTR binding as those observed following EE. Conversely, repeated administration of the OTR antagonist L,369-899 (5 mg/kg/day) during EE exposure, but not during the acquisition of alcohol CPP, reversed the pronounced EE-induced ethanol rewarding effect. These results demonstrate for the first time, a stimulatory effect of environmental enrichment exposure on alcohol reward via an oxytocinergic-dependent mechanism, which may predispose to alcohol abuse. This study offers a unique prospective on the neurobiological understanding of the initial stages of alcohol use/misuse driven by complex environmental-social interplay. (C) 2018 Elsevier Ltd. All rights reserved. (AU)

FAPESP's process: 12/09854-0 - Effects of environmental enrichment on ethanol induced behaviors in Swiss mice: role of stress circuitry
Grantee:Mariana Beu Rae
Support Opportunities: Scholarships in Brazil - Master
FAPESP's process: 12/50207-8 - Effects and neurobiological mechanisms of environmental manipulations on ethanol and nicotine induced behavioural effects: involvement of the stress circuitry
Grantee:Rosana Camarini
Support Opportunities: Regular Research Grants
FAPESP's process: 15/02397-0 - Study of environmental enrichment inducing a protective phenotype of behaviors that assess addictive features in mice
Grantee:Rosana Camarini
Support Opportunities: Regular Research Grants