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Reduction of ethanol intake by corticotropin-releasing factor receptor-1 antagonist in “heavy-drinking” mice in a free-choice paradigm

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Abstract

Rationale

We hypothesized that the corticotropin-releasing factor (CRF) system is hyperresponsive in animals with high ethanol intake, which exhibits a reduction of ethanol intake when administered with a CRF1 receptor antagonist.

Methods

Outbred Swiss mice were subjected to a long-term, three-bottle, free-choice paradigm (5 and 10 % [v/v] ethanol and water) that consisted of four phases: acquisition (AC; 10 weeks), withdrawal (W; 2 weeks), reexposure (RE; 2 weeks), and quinine-adulteration (AD; 2 weeks). Based on individual ethanol intake, the mice were classified into three groups: A group, preference for ethanol and persistently high consumption during AD phase; B group, preference for ethanol and a reduction of ethanol intake in the AD phase; and C group; preference for water during all phases. A control group only had access to water. CRF1 receptor messenger RNA (mRNA) levels in the amygdala and the effect of the CRF1 receptor antagonist CP-154,526 on ethanol and water intake in the subgroups were studied.

Results

CRF1 transcript levels were higher in the B group than in the control group. The highest dose of CP-154,526 reduced ethanol intake and preference, with no changes in water consumption, in the A group compared with vehicle. The B group exhibited a reduction of both ethanol and water intake, with no changes in preference. The C group exhibited no changes in response to the CRF1 antagonist.

Conclusions

CRF1 receptors appear to be involved in ethanol consumption in mice with high ethanol consumption, and CRF system-mediated neuroadaptations depend on drinking profiles.

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Acknowledgments

We thank Silvia N.C. Genaro, Vania D’Almeida, Olga M. Chaim, and Luthi Grassi for the technical assistance; Michael A. Arends for his assistance with the revision of the MS; and Pfizer Laboratories for the donation of CP-154,526. The study was supported by UFPR and FAPESP. DC, BJM, AFR, MP, and IPS were recipients of fellowships from CAPES, and RBL and RC were recipients of fellowships from CNPq.

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Authors and Affiliations

  1. Departamento de Farmacologia, Jardim das Américas, Universidade Federal do Paraná, P.O. Box 19031, Curitiba, PR, 81531-990, Brazil

    Diego Correia, Bruno Jacson Martynhak, Marcela Pereira, Isadora Pozzetti Siba & Roseli Boerngen-Lacerda

  2. Programa de Pós-Graduação em Neurociências, Faculdade de Filosofia de Ciências Humanas, Universidade Federal de Minas Gerais, Minas Gerais, MG, 31270-901, Brazil

    Andrea Frozino Ribeiro

  3. Departamento de Farmacologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, 05508-900, Brazil

    Rosana Camarini

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  1. Diego Correia
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  2. Bruno Jacson Martynhak
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  3. Marcela Pereira
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  4. Isadora Pozzetti Siba
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  7. Roseli Boerngen-Lacerda
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Correspondence to Roseli Boerngen-Lacerda.

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Correia, D., Martynhak, B.J., Pereira, M. et al. Reduction of ethanol intake by corticotropin-releasing factor receptor-1 antagonist in “heavy-drinking” mice in a free-choice paradigm. Psychopharmacology 232, 2731–2739 (2015). https://doi.org/10.1007/s00213-015-3909-y

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  • DOI: https://doi.org/10.1007/s00213-015-3909-y

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