Modulation of the mesolimbic dopaminergic system by beta-endorphin-(1-27) as assessed by microdialysis

Abstract

In the present study we used in vivo microdialysis to examine the influence of beta-endorphin-(1-27) (beta-EP-(1-27) upon beta-endorphin (beta-EP)-induced dopamine (DA) release in the nucleus accumbens of anesthetized rats. Microdialysis probes were inserted into the nucleus accumbens and perfusates were analyzed for DA and its metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), using a reversed-phase HPLC system with electrochemical detection. Intracerebroventricular (i.c.v.) administration of beta-EP-(1-27) (5-20 micrograms) resulted in a dose-dependent increase in DA release which was smaller than the beta-EP-induced DA release, whereas metabolite levels were not altered. Pretreatment with beta-EP-(1-27) (5-20 micrograms) significantly altered the beta-EP (5 micrograms)-induced increase in DA release. These results indicate that beta-EP-(1-27) antagonizes the beta-EP-induced release of DA in the nucleus accumbens. In addition to its antagonistic properties at the beta-endorphin binding site, beta-EP-(1-27) appears to be a partial agonist, inducing increased DA release. These findings suggest a regulatory function for this naturally occurring beta-EP fragment within the mesolimbic system.