Involvement of the enkephalinergic system in the dopamine sensitization to cocaine in the nucleus accumbens.

BETHANIA MONGI BRAGATO; CONSTANZA GARCIA KELLER; ASSIS M.A; ANDREAS ZIMMER; LILIANA ANCELA

Huerta Grande

Congreso; XXVII Annual Congress of the Argentine Society of Neurosciences (SAN), Huerta Grande. Córdoba; 2012

SAN

Endogenous opioid peptides, mainly enkephalin, are largely distributed in the mesolimbic system. However, their contribution to cocaine - induced sensitization on behavioral and neurochemical parameters has been poorly studied. 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 done: I) Microdialysis: dopamine extracellular levels were measured by HPLC in nucleus accumbens in response to saline and cocaine challenge (7,5mg/Kg). II) Immunohistochemistry: met enkephalin levels were determined in nucleus accumbens and striatum in response to saline and cocaine challenge. Our results demonstrated that Penk KO mice did not show sensitization to the neurochemical effects induced by cocaine, as it was shown in wild type mice treated chronically with the drug. Despite the fact that dopamine levels in response to an acute dose of cocaine was similar in both genotypes. Concurrently, wild type mice evidenced an increase in met-enkephalin levels induced by cocaine treatment in nucleus accumbens and striatum. 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.