Up-regulated dopamine D1 receptor binding can be detected in vivo following repeated SCH 23390, but not SKF 81297 or 6-hydroxydopamine, treatments

• Published in: European journal of pharmacology Vol. 459; no. 2; pp. 195 - 201
• Main Authors: Schwartz, Robert A., Greenwald, Eric R., Fletcher, Paul J., Houle, Sylvain, DaSilva, Jean N.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 17-01-2003; Elsevier
• Subjects: Animals; Apomorphine; Benzazepines - administration & dosage; Biological and medical sciences; cAMP-mediated signaling pathway; Catecholaminergic system; Male; Medical sciences; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Oxidopamine - administration & dosage; PET (positron emission tomography); Pharmacology. Drug treatments; Protein Binding - drug effects; Protein Binding - physiology; Rats; Rats, Sprague-Dawley; Receptor supersensitivity; Receptors, Dopamine D1 - agonists; Receptors, Dopamine D1 - antagonists & inhibitors; Receptors, Dopamine D1 - metabolism; Up-regulation; Up-Regulation - drug effects; Up-Regulation - physiology; Uptake; Receptor supersensitivity; cAMP-mediated signaling pathway; PET (positron emission tomography); Apomorphine; Uptake; Up-regulation; Agonist; Molecular form; Rat; Central nervous system; Oxidopamine; Signal transduction; Subcutaneous administration; Sensitization; Mechanism of action; Hypersensitivity; Rodentia; D1 Dopamine receptor; Cyclic AMP; Corpus striatum; Sympathomimetic; Vertebrata; Biological fixation; Mammalia; Animal; Comparative study; Brain (vertebrata)
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(02)02850-9

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-1
H-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-1
H-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.