Morphine-induced alterations of local cerebral glucose utilization in the basal ganglia of rats.
The actions of various doses of morphine on the local cerebral glucose utilization (LCGU) were studied by means of the autoradiographic [14C]2-deoxyglucose technique. Morphine (1-15 mg/kg i.p.) decreased LCGU in most areas of the basal ganglia (caudate nucleus, globus pallidus, nucleus accumbens), but not in the substantia nigra pars compacta. LCGU was also decreased in limbic nuclei, such as septum, hippocampus and amygdala, and in most thalamic areas. In most cortical regions, a decrease was found as well. Findings in some efferent nuclei seemed of particular interest, namely in the substantia nigra pars reticulata, anteroventral and lateral nucleus of the thalamus and the subthalamic nucleus, where decreases in LCGU were found after administration of 7.5 mg/kg or sometimes lower doses, but not after 15 mg/kg of morphine. The decreases seem to reflect a general depressory effect of morphine on neuronal activity which is known from electrophysiological studies. Part of these effects might be, in addition, due to an activation of dopaminergic neurons, since dopamine mainly acts as an inhibitory neurotransmitter. This dopaminergic activation leads to characteristic behavioral effects after lower doses of morphine. The largest dose used (15 mg/kg) produces muscular rigidity, probably by a direct action on the striatum. This effect antagonizes and masks the dopaminomimetic effects. The results suggest that it also antagonizes the functional alterations in some efferent nuclei of the basal ganglia manifest after lower doses of morphine. Local injections of morphine (15 micrograms) led to decreases of LCGU in the various parts of the striatum, but to increases in lateral and anteroventral thalamus.(ABSTRACT TRUNCATED AT 250 WORDS)
Beck
T
T
Institute for Pharmacology and Toxicology, Faculty of Pharmacy, University of Marburg, F.R.G.
Wenzel
J
J
Kuschinsky
K
K
Krieglstein
J
J
D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002250:Carbon Radioisotopes; D003837:Deoxy Sugars / Q000378:metabolism*; D003847:Deoxyglucose / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D011865:Radioisotope Dilution Technique; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D002250:Carbon Radioisotopes; D003837:Deoxy Sugars; D009270:Naloxone; D009020:Morphine; D003847:Deoxyglucose