BIOCHEMICAL ADAPTATIONS IN THE MESOLIMBIC DOPAMINE SYSTEM IN RESPONSETO HEROIN SELF-ADMINISTRATION

Previous studies have shown that chronic, forced exposure to opiates p roduces specific biochemical adaptations in the ventral tegmental area (VTA) and nucleus accumbens (NAc). The functional consequences of the se adaptations have been hypothesized to contribute to certain motivat ional aspects of drug addiction. In this study, the possibility that s imilar adaptations could occur in response to intermittent heroin self -administration was tested by comparing homogenates of VTA and NAc fro m rats self-administering heroin, rats receiving yoked injections of h eroin, and rats receiving yoked injections of saline (controls). Tyros ine hydroxylase (TH) immunoreactivity was increased (31-38%) in the VT A and decreased (11%) in the NAc of heroin-exposed rats relative to co ntrols. Heroin exposure also increased cAMP-dependent protein kinase ( PKA) activity in both particulate (19-27%) and soluble (17-20%) fracti ons of the NAc, and decreased (16-17%) the level of G(i alpha) immunor eactivity in this brain region. In contrast, no significant biochemica l changes were found in the substantia nigra or caudate-putamen, indic ating a selective effect on the mesolimbic dopamine system. Overall, a daptations in the VTA and NAc of heroin-exposed rats were similar to, but generally smaller in magnitude than, adaptations produced by chron ic morphine administration. However, in contrast to morphine-treated a nimals, heroin-exposed animals failed to display overt signs of opiate physical dependence, suggesting that adaptations in motivational syst ems may occur more readily than adaptations in brain regions associate d with physical dependence. (C) 1995 Wiley-Liss, Inc.