ALTERATION OF LOCAL CEREBRAL GLUCOSE-UTILIZATION FOLLOWING INTRAVENOUS ADMINISTRATION OF HEROIN IN FISCHER-344 RATS

The 2-deoxyglucose method was used to study the effects of acute admin istration of small intravenous doses of heroin on rates of glucose uti lization in rat brain to identify small brain regions that may be invo lved in the acute behavioral effects of heroin. In contrast to previou s studies which have used relatively large doses, the doses of heroin used in this study have been shown to be self-administered [Martin, T. J., Dworkin, S.I. and Smith, J.E., Alkylation of mu-opioid receptors b y beta-funaltrexamine in vivo: comparison of the effects on in situ bi nding and heroin self-administration in rats., J. Pharmacol. Exp. Ther ., 272 (1995) 1135-1140.]. Administration of 18 mu g/kg of heroin resu lted in higher rates of glucose utilization in the medial olfactory tu bercle, anterior nucleus accumbens and dorsolateral caudate while havi ng no other effects on limbic structures compared to saline-treated an imals. Conversely, the rate of glucose utilization was lower than cont rol in the habenula, dorsal raphe, and central gray following adminstr ation of 18 mu g/kg of heroin. Administration of two higher doses (60 and 100 mu g/kg) resulted in lower rates of glucose utilization in the thalamus, habenula, inferior colliculus, dorsal raphe and central gra y compared to saline. The higher rates of glucose utilization in the l imbic areas were specific for the lowest dose of heroin, whereas the e ffect of lowering the rate of glucose utilization compared to control in the thalamus and inferior colliculus were an increasing function of dose. In the habenula and dorsal raphe, however, the dose-effect func tion was inverted. These data indicate that the alterations of glucose utilization in rat brain by heroin are site-specific and the systems involved as well as the nature of the alteration differs for individua l doses of heroin.