PET imaging of striatal dopamine D2 receptors in nonhuman primates: increases in availability produced by chronic raclopride treatment.
Previous research using positron emission tomography (PET) in monkeys has shown that attaining social dominance can result in increased DA D2 receptor availability and attenuated sensitivity to the reinforcing effects of cocaine. The present study utilized a within-subjects design to determine whether chronic treatment with the D2 receptor antagonist raclopride could similarly increase D2 receptor availability. Using the D2-selective radioligand [(18)F]fluoroclebopride (FCP), three adult male cynomolgus monkeys were scanned before and after chronic treatment with raclopride (0.01 mg/kg per h for 30 +/- 1 day) administered by a subcutaneous osmotic pump. Food-reinforced operant behavior was assessed during treatment. A transitory decrease in responding was observed during the initial eight days of raclopride treatment. Tolerance developed by the tenth session, and responding remained at baseline levels for the duration of treatment and after treatment was discontinued. Averaged across monkeys, chronic raclopride administration increased FCP distribution volume ratios (DVRs) between 12 and 20% in the caudate nucleus, putamen, and anterior cingulate cortex. When monkeys were re-scanned 9-12 months after termination of raclopride treatment, FCP DVRs remained elevated in two subjects, and decreased below baseline levels in the third monkey. Considering the reported 2% test/retest variability for FCP, these findings indicate that chronic treatment with a D2 receptor antagonist can produce large increases in D2 receptor availability as measured with PET. Individual differences in rates of recovery were observed, such that the increases in DVR persisted in two of three subjects.
Czoty
Paul W
PW
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Gage
H Donald
HD
Nader
Michael A
MA
D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology*; D008252:Macaca fascicularis; D008297:Male; D049268:Positron-Emission Tomography; D020891:Raclopride / Q000494:pharmacology*; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors
D018492:Dopamine Antagonists; D017448:Receptors, Dopamine D2; D020891:Raclopride