COCAINE INDUCED DOPAMINE SENSITIZATION IS ABSENT IN MICE LACKING THE PRE - PROENKEPHALIN GENE.

MOGI BRAGATO, B; GARCÍA KELLER, C; ASSIS, M.A; ANDREAS ZIMMER; LILIANA CANCELA

Workshop; II International Workshop Motivated, behavior, stress and addiction: from molecules to behavior; 2012

Endogenous opioid peptides, mainly enkephalin, are largely distributed in the mesolimbic system. However, their contribution to cocaine-induced behavioral and neurochemical sensitization has been poorly studied. The aim of this study was to demonstrate the involvement of enkephalin on the dopamine sensitization to cocaine and its correlation with the met-enkephalin levels in the nucleus accumbens. Male C57B/6J wild type (WT) and preproenkephalin knockout (KO Penk) mice were daily treated with cocaine (15mg/Kg i.p.) and vehicle for 9 days. On day 21 of the treatment the following experiments were performed: I) Microdialysis: dopamine extracellular levels were measured by HPLC in nucleus accumbens in response to saline and cocaine challenge (7,5 mg/Kg). II) Immunohistochemistry: met enkephalin levels were determined in nucleus accumbens and striatum in response to saline and cocaine challenge. Our results demonstrated that KO Penk mice did not show sensitization to the cocaine-induced dopamine release, as it was shown in wild type mice treated chronically with the drug. It should be noted that dopamine levels in response to an acute dose of cocaine was similar in both genotypes. Concurrently, wild type mice evidenced an enhancement of cocaine-induced increase in met-enkephalin levels in nucleus accumbens and striatum following chronic treatment with the drug. These results indicate that enkephalinergic system is strongly involved in the dopamine sensitization to cocaine in the nucleus accumbens from animals chronically treated with cocaine.