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 administration of small intravenous doses of heroin on rates of glucose utilization in rat brain to identify small brain regions that may be involved in the acute behavioral effects of heroin. In contrast to previous 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 by beta-funaltrexamine in vivo: comparison of the effects on in situ binding and heroin self-administration in rats., J. Pharmacol. Exp. Ther., 272 (1995) 1135-1140.]. Administration of 18 microg/kg of heroin resulted in higher rates of glucose utilization in the medial olfactory tubercle, anterior nucleus accumbens and dorsolateral caudate while having no other effects on limbic structures compared to saline-treated animals. Conversely, the rate of glucose utilization was lower than control in the habenula, dorsal raphe, and central gray following adminstration of 18 microg/kg of heroin. Administration of two higher doses (60 and 100 microg/kg) resulted in lower rates of glucose utilization in the thalamus, habenula, inferior colliculus, dorsal raphe and central gray compared to saline. The higher rates of glucose utilization in the limbic areas were specific for the lowest dose of heroin, whereas the effect 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 function 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 individual doses of heroin.
Martin
T J
TJ
Center for the Neurobiological Investigation of Drug Abuse, Department of Physiology and Pharmacology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC 27157-1083, USA. tjmartin@isnet.is.wfu.edu
Miller
M
M
Dworkin
S I
SI
Smith
J E
JE
Porrino
L J
LJ
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D005947:Glucose / Q000378:metabolism*; D003932:Heroin / Q000494:pharmacology*; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D012646:Self Administration
D000701:Analgesics, Opioid; D003932:Heroin; D005947:Glucose