Stress Abolishes the Effect of Previous Chronic Ethanol Consumption on Drug Place Preference and on the Mesocorticolimbic Brain Pathway

Authors

  • Daniel Moreira-Silva,

    1. Institute of Biomedical Sciences , Federal University of Uberlândia (UFU), Uberlândia, Brazil
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  • Gessynger Morais-Silva,

    1. Institute of Biomedical Sciences , Federal University of Uberlândia (UFU), Uberlândia, Brazil
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  • Juliana Fernandes-Santos,

    1. Institute of Biomedical Sciences , Federal University of Uberlândia (UFU), Uberlândia, Brazil
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  • Cleopatra S. Planeta,

    1. Laboratory of Pharmacology , School of Pharmaceutical Sciences, Univ. Estadual Paulista (UNESP), Araraquara, Brazil
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  • Marcelo T. Marin

    Corresponding author
    1. Institute of Biomedical Sciences , Federal University of Uberlândia (UFU), Uberlândia, Brazil
    2. Laboratory of Pharmacology , School of Pharmaceutical Sciences, Univ. Estadual Paulista (UNESP), Araraquara, Brazil
    • Reprint requests and Present address: Marcelo T. Marin, Depto. Princípios Ativos Naturais e Toxicologia (PANT), Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista (UNESP), Rod. Araraquara-Jaú km 01, CEP 14801-902, Araraquara, SP, Brazil; Tel.: +55-16-3301-6984; Fax: +55-16-3322-0073; E-mail: marcelo@fcfar.unesp.br

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Abstract

Background

Conditioned place preference (CPP) to ethanol (EtOH) is an important addiction-related alteration thought to be mediated by changed neurotransmission in the mesocorticolimbic brain pathway. Stress is a factor of major importance for the initiation, maintenance, and reinstatement of drug abuse and modulates the neurochemical outcomes of drugs. Thus, the aim of this study was to investigate the effects of concomitant exposure to chronic EtOH and stress on CPP to this drug and alterations of dopaminergic and serotonergic neurotransmission in mice.

Methods

Male Swiss mice were chronically treated with EtOH via a liquid diet and were exposed to forced swimming stress. After treatment, animals were evaluated for conditioning, extinction, and reinstatement of CPP to EtOH. Also, mice exposed to the same treatment protocol had their prefrontal cortex (PFC), nucleus accumbens (NAc), and amygdala dissected for the quantitation of dopamine, serotonin, and their metabolites content.

Results

Data showed that previous chronic exposure to EtOH potentiated EtOH conditioning and increased dopaminergic turnover in PFC. Exposure to stress potentiated EtOH conditioning and decreased dopaminergic turnover in the NAc. However, animals exposed to both chronic EtOH and stress did not display alterations of CPP and showed an elevated content of dopamine in amygdala. No treatment yielded serotonergic changes.

Conclusions

The present study indicates that previous EtOH consumption as well as stress exposure induces increased EtOH conditioning, which can be related to dopaminergic alterations in the PFC or NAc. Interestingly, concomitant exposure to both stimuli abolished each other's effect on conditioning and PFC or NAc alterations. This protective outcome can be related to the dopaminergic increase in the amygdala.

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