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

GIMENA GOMEZ; JEAN LUD CADET; VERONICA BISAGNO; JAVIER A. MUÑIZ ; MARÍA CELESTE RIVERO-ECHETO; BETINA GONZÁLEZ; FRANCISCO J. URBANO; EDGAR GARCÍA-RILL

NEUROTOXICITY RESEARCH

SPRINGER

Lugar: Berlin; Año: 2016

1029-8428

Caffeine is the world?s most popular psy-choactive drug and is also an active adulterant found inmany drugs of abuse, including seized cocaine samples.Despite several studies which examine the effects of caf-feine or cocaine administered as single agents, little dataare available for these agents when given in combination.The purpose of the present study was to determine ifcombined intake of both psychostimulants can lead tomaladaptive changes in striatal function. Mice wereinjected with a binge regimen (intermittent treatment for13 days) of caffeine (395 mg/kg), cocaine (3910 mg/kg), or combined administration. We found that chroniccaffeine potentiated locomotion induced by cocaine andthat both caffeine-treated groups showed sensitization.Striatal tissue was obtained 24 h and 7 days after lastinjection (withdrawal) for immunohistochemistry andmRNA expression. Our results show that combined intakeof both psychostimulants can increase GFAP immunore-activity in the striatum at both times post treatment. Geneexpression analysis, targeted at dopamine, adenosine, andglutamate receptor subunit genes, revealed significanttranscript down-regulation in the dorsal striatum of AMPA,NMDA, D1 and D2 receptor subunit mRNA expression inthe group that received combined treatment, but not afterindividual administration. At withdrawal, we foundincreased D1 receptor mRNA expression along withincreased A1, AMPA, NMDA, and metabotropic subunitexpression. A2A mRNA showed decreased expressionafter both times in all experimental groups. Our studyprovides evidence that there are striatal alterations medi-ated by combined caffeine and cocaine administration, andhighlights negative outcomes of chronic intake of bothpsychostimulants.