Disinhibition of nucleus accumbens neurons by the dopamine D2 receptor agonist LY-141865: prevented by 6-OHDA pretreatment.

Intravenous administration of LY-141865, a specific dopamine (DA) D2 receptor agonist, caused a biphasic increase/decrease in the firing rate of cells in the rat nucleus accumbens (NAc). 6-Hydroxydopamine injected directly into the medial forebrain bundle, through which the ascending DA fibers pass, prevented the initial rate increase of NAc neurons produced by low doses of LY-141865. In contrast, pretreatment of rats with 5,7-dihydroxytryptamine did not alter the biphasic response of NAc neurons to LY-141865. These results, together with previous findings that D2 autoreceptors are much sensitive to DA and DA agonists, strongly support the hypothesis that the initial rate-increase caused by low doses of LY-141865 is the result of disinhibition.