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Combined Effects of Simultaneous Exposure to Caffeine and Cocaine in the Mouse Striatum

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Abstract

Caffeine is the world’s most popular psychoactive drug and is also an active adulterant found in many drugs of abuse, including seized cocaine samples. Despite several studies which examine the effects of caffeine or cocaine administered as single agents, little data are available for these agents when given in combination. The purpose of the present study was to determine if combined intake of both psychostimulants can lead to maladaptive changes in striatal function. Mice were injected with a binge regimen (intermittent treatment for 13 days) of caffeine (3 × 5 mg/kg), cocaine (3 × 10 mg/kg), or combined administration. We found that chronic caffeine potentiated locomotion induced by cocaine and that both caffeine-treated groups showed sensitization. Striatal tissue was obtained 24 h and 7 days after last injection (withdrawal) for immunohistochemistry and mRNA expression. Our results show that combined intake of both psychostimulants can increase GFAP immunoreactivity in the striatum at both times post treatment. Gene expression analysis, targeted at dopamine, adenosine, and glutamate receptor subunit genes, revealed significant transcript down-regulation in the dorsal striatum of AMPA, NMDA, D1 and D2 receptor subunit mRNA expression in the group that received combined treatment, but not after individual administration. At withdrawal, we found increased D1 receptor mRNA expression along with increased A1, AMPA, NMDA, and metabotropic subunit expression. A2A mRNA showed decreased expression after both times in all experimental groups. Our study provides evidence that there are striatal alterations mediated by combined caffeine and cocaine administration, and highlights negative outcomes of chronic intake of both psychostimulants.

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Acknowledgements

Dr. Bisagno has been authorized to study drug abuse substances in animal models by A.N.M.A.T. (National Board of Medicine Food and Medical Technology, Ministerio de Salud, Argentina). This work was supported by FONCYT-Agencia Nacional de Promoción Científica y Tecnológica; BID 1728 OC.AR. T 2012-0924 Argentina (to Dr. Bisagno) and FONCYT-Agencia Nacional de Promoción Científica y Tecnológica; BID 1728 OC.AR. PICT-2012-1769, Argentina, and UBACYT 2014-2017 #20120130101305BA (to Dr. Urbano). In addition, this work was supported by core facilities of the Center for Translational Neuroscience, UAMS, USA, supported by NIH award P20 GM110702.

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    1. Instituto de Investigaciones Farmacológicas (Universidad de Buenos Aires—Consejo Nacional de Investigaciones Científicas y Técnicas), Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina

      Javier A. Muñiz, Gimena Gomez, Betina González & Veronica Bisagno

    2. Laboratorio de Fisiología y Biología Molecular, Instituto de Fisiología, Biología Molecular y Neurociencias, Departamento de Fisiología, Biología Molecular y Celular “Dr. Hector Maldonado” (DFBMC), Universidad de Buenos Aires—Consejo Nacional de Investigaciones Científicas y Técnicas, Junín 956, piso 5, Ciudad Autónoma de Buenos Aires, C1113, Buenos Aires, Argentina

      María Celeste Rivero-Echeto & Francisco J. Urbano

    3. Molecular Neuropsychiatry Research Branch, NIH/NIDA Intramural Research Program, Baltimore, MD, USA

      Jean Lud Cadet

    4. Department of Neurobiology and Developmental Sciences, Center for Translational Neuroscience, University of Arkansas for Medical Sciences, Little Rock, AR, USA

      Edgar García-Rill

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    1. Javier A. Muñiz
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    Correspondence to Veronica Bisagno.

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    Javier A. Muñiz and Gimena Gomez have contributed equally to this work.

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    Muñiz, J.A., Gomez, G., González, B. et al. Combined Effects of Simultaneous Exposure to Caffeine and Cocaine in the Mouse Striatum. Neurotox Res 29, 525–538 (2016). https://doi.org/10.1007/s12640-016-9601-0

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