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

MONGI BRAGATO B; CONSTANZA GARCIA KELLER; ASSIS A; ZIMMER A; CANCELA LILIANA

Congreso; XXVII Annual Congress of the Argentine Society of Neurosciences (SAN); 2012

Endogenous opioidpeptides, mainly enkephalin, are largely distributed in the mesolimbic system. 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. Penk KO mice did not show sensitization to the behavioraleffects induced by cocaine and failed to show the cocaine-induced increases in ERK activation and AMPA cell surfaceexpression evidenced in the WT mice. However, the locomotor activity inresponse to an acute injection of the drug and the levels of dopaminetransporter were similar in both KO and WT mice. Wild type mice pretreated withnaloxone did not show the cocaine - induced increased in ERK and CREBphosphorilation. These results indicate that preproenkephalin-derived opioid peptides,possibly through the activation of opioid receptors in mesolimbic areas, arestrongly involved in the long-term plasticity underlying behavioralsensitization to cocaine.