D1 dopamine agonist and antagonist effects on regional cerebral glucose utilization in rats with intact dopaminergic innervation.
The effects of stimulation and blockade of the D1 dopamine receptor on regional cerebral glucose utilization (RCGU) were studied using quantitative [14C]2-deoxyglucose autoradiography in naive rats. Systemic administration of the selective D1 antagonist, SCH 23390 (0.5 mg/kg), lowered glucose utilization by 24-28% in the globus pallidus, entopeduncular nucleus, subthalamic nucleus, substantia nigra pars reticulata (SNr), and motor cortex, suggesting that stimulation of the D1 receptor by endogenous dopamine contributes to basal metabolism in these regions. Administration of SCH 23390 increased RCGU in the lateral habenula, as do selective D2 antagonists. The selective D1 agonist, SKF 38393 (30 mg/kg), increased RCGU in the SNr (up 22%) without affecting the other brain regions which were examined. This modest increase contrasts with the large increase in RCGU (up 100-200%) in the SNr elicited by similar doses of SKF 38393 in rats with acute or chronic dopamine depletion. Systemic administration of amphetamine (5.0 mg/kg), a dopamine releasing agent, increased RCGU in the caudate-putamen (up 33%), globus pallidus (up 23%), subthalamic nucleus (up 46%), entopeduncular nucleus (up 78%), and SNr (up 72%) and lowered RCGU in the lateral habenula (down 43%). All of these amphetamine effects were blocked by pretreatment with either SCH 23390 (0.5 mg/kg) or eticlopride (2.0 mg/kg, a selective D2 antagonist). These results suggest that endogenous dopamine stimulates both D1 and D2 receptors in vivo and provide metabolic evidence to support the concept of a functional linkage of D1 and D2 receptor systems in animals with intact dopaminergic innervation.
Trugman
J M
JM
Department of Neurology, University of Virginia School of Medicine, Charlottesville 22908.
James
C L
CL
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D001479:Basal Ganglia / Q000166:cytology / Q000187:drug effects; D001552:Benzazepines / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects*; D003847:Deoxyglucose / Q000378:metabolism; D004298:Dopamine / Q000502:physiology*; D005947:Glucose / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors* / Q000187:drug effects*; D012457:Salicylamides / Q000494:pharmacology
D001552:Benzazepines; D017447:Receptors, Dopamine D1; D012457:Salicylamides; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D003847:Deoxyglucose; D000661:Amphetamine; D005947:Glucose; C045989:eticlopride; D004298:Dopamine