Up-regulated dopamine D1 receptor binding can be detected in vivo following repeated SCH 23390, but not SKF 81297 or 6-hydroxydopamine, treatments.
Three different pharmacological treatments, previously shown to cause dopamine D1 receptor supersensitivity in rats, were studied for changes in the binding of R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SCH 23390) labeled with carbon-11. Rats treated subchronically with the full dopamine D1 receptor agonist R/S-(+/-)-6-chloro-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SKF 81297) showed no significant difference in dopamine D1 receptor binding. Similarly, unilateral 6-hydroxydopamine lesioning, followed by apomorphine screening for contralateral rotation, failed to cause significant differences in the rat brain distribution of [11C]SCH 23390 in the lesioned versus the nonlesioned striatal sides. In contrast, repeated exposure with the dopamine D1 receptor antagonist SCH 23390 significantly enhanced the uptake of [11C]SCH 23390 in the dopamine D1 receptor-rich striatum and olfactory tubercles. These results demonstrate that [11C]SCH 23390 can significantly detect enhanced binding in rat brain regions expected to have up-regulated dopamine D1 receptors. The failure of [11C]SCH 23390 to reveal any differences after subchronic agonist or 6-hydroxydopamine treatments suggests that the behavioural supersensitization induced by these treatments is possibly due to changes to the high-affinity state or to components downstream of dopamine D1 receptors in the signal transduction pathway. The present study has implications for studies imaging dopamine D1 receptors in neuropsychiatric disorders with abnormal dopamine stimulation using positron emission tomography.
Schwartz
Robert A
RA
PET Centre, Centre for Addiction and Mental Health, 250 College Street, M5T 1R8, Toronto, Ontario, Canada.
Greenwald
Eric R
ER
Fletcher
Paul J
PJ
Houle
Sylvain
S
DaSilva
Jean N
JN
D000818:Animals; D001552:Benzazepines / Q000008:administration & dosage*; D008297:Male; D016627:Oxidopamine / Q000008:administration & dosage*; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects* / Q000502:physiology
D001552:Benzazepines; D017447:Receptors, Dopamine D1; C067113:SK&F 81297; D016627:Oxidopamine