CHRONIC CAFFEINE AND COCAINE ADMINISTRATION INDUCES LOCOMOTOR SENSITIZATION AND REDUCED MRNA EXPRESSION OF DOPAMINE, ADENOSINE AND GLUTAMATE RECEPTORS IN THE MOUSE STRIATUM.

JAVIER A. MUÑIZ; BETINA GONZALEZ; MARIA CELESTE RIVERO-ECHETO; JEAN LUD CADET; EDGAR GARCIA-RILL; FRANCISCO URBANO; VERONICA BISAGNO

Rio de Janeiro

Congreso; IBRO 2015 9th world congress; 2015

International Brain Research Organization

Chronic psychostimulant intake can cause neuroplasticity and toxic consequences in dopaminergic brain areas. Recreational use of psychostimulants such as cocaine (Coc) is often abused in combination with other psychostimulants like caffeine (Caf). In the present study we evaluated the effects of Coc, Caf, and their combination in mice. Male C57/BL-6 mice were treated with Coc (10 mg/kg), Caf (5mg/kg), their combination (Caf-Coc) (10 mg/kg Coc + 5 mg/kg Caf) or vehicle (Veh), in an intermittent binge protocol (3 i.p. injections, 1 h apart, one day on/off for 13 days). We investigated the effects of both psychostimulants on locomotor activity at day 1 (acute) and day 13th (chronic). Acute Caf and Coc administration induced hyperlocomotion; the Caf-Coc group showed higher locomotor activity compared to the Caf group but not to Coc group. Chronic administration (at day 13) increased locomotor activity compared to their acute responses (day 1): Coc, Caf and Caf-Coc groups showed significantly different values compared to Vehicle; CC5 group exhibited higher locomotion than any other group at day 13. Also, we have found that the Caf-Coc group showed locomotor sensitization. One day after treatments, animals were sacrificed and striatal tissue was dissected for Western Blot and cPCR analysis. We found that Coc, and Caf-Coc increased the expression of Tyrosine Hydroxylase (TH) and that the group that received both psychostimulants combined was the only one that showed increased Histone deacetylase 2 (HDAC2) expression. Deacetylation by HDACs at lysine residues are widely studied histone post-translational modifications in various neuropsychiatric diseases, including addiction. Thus, we investigated whether both psychostimulants might differentially regulate gene expression in the striatum. We found that both Coc and Caf-Coc groups showed decreased glutamate AMPA receptor (Gria1) but only the Caf-Coc showed decreased D1 (Drd1a) and D2 (Drd2) dopamine receptors. All groups that received psychostimulants showed reduced expression of A2A (Adora2a) adenosine receptor.Our results show that: i) Caf is able to potentiate Coc locomotor effects, ii) chronic Coc treatment induces increased in TH expression in the striatum, iii) chronic administration with both psychostimulants increased HDAC2 expression and altered the expression of glutamate, dopamine and adenosine receptors in the striatum. Increased HDAC2 expression has been associated with other conditions involving toxicity and neurodegeneration in the CNS. Altogether, our results suggest negative consequences of the combined intake of cocaine and caffeine on the striatum. Further experiments are warranted to investigate the extent of this negative outcome as well as possible deficits on cortico-striatal networks.