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

In the present study we used in vivo microdialysis to examine the influence of β-endorphin-(1-27) (β-EP-(1-27) upon β-endorphin (β-EP)-induced dopamine (DA) release in the nucleus accumbens of anesthetized rats. Microdialysis probes were inserted into the nucleus accumbens and peifusates 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 β-EP-(1-27) (5-20 μg) resulted in a dose-dependent increase in DA release which was smaller than the β-EP-induced DA release, whereas metabolite levels were not altered. Pretreatment with β-EP-(1-27) (5-20 μg) significantly altered the β-EP (5 μg)-induced increase in DA release. These results indicate that β-EP-(1-27) antagonizes the β-EP-induced release of DA in the nucleus accumbens. In addition to its antagonistic properties at the β-endorphin binding site, β-EP-(1-27) appears to be a partial agonist, inducing increased DA release. These findings suggest a regulatory function for this naturally occurring β-EP fragment within the mesolimbic system.