Agonist action of the agonist/antagonist analgesic butorphanol on dopamine metabolism in the nucleus accumbens of the rat

Abstract

The action of butorphanol, an opiate agonist/antagonist, was studied on dopamine (DA) metabolism in several mesocortical and mesolimbic areas and compared with its effects on the nigrostriatal DA pathway. While butorphanol had a bell-shaped dose-response relationship for elevation of DA metabolites in the striatum, it had no action on DA metabolites in the entorhinal, prefrontal, pyriform and cingulate cortices and in the olfactory tubercle. In all of these areas morphine stimulated dopamine metabolism (except for the entorhinal cortex). In contrast, in the nucleus accumbens, butorphanol increased the levels of dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 3-methoxytyramine (3-MT) with no increase in DA steady state levels. This effect was reversible by both opiate antagonists, naloxone and WIN 44441-3 and appears to be μ-opioid receptor-mediated.