title: Labeling in vivo of serotonin uptake sites in rat brain after administration of [3H]cyanoimipramine.
abstract: The properties of sites in rat brain labeled in vivo after administration of [3H]cyanoimipramine ([3H]CN-IMI) have been studied. The radioactivity in hypothalamus and cortex 20 min to 2 hr after [3H]CN-IMI administration was reduced in rats pretreated with chlorimipramine (10 mg/kg) 5 min before [3H]CN-IMI. No effect of chlorimipramine pretreatment was seen in the cerebellum; levels of radioactivity in this tissue were subtracted from total levels in hypothalamus and cortex to define specific binding. This represented approximately 50 and 30% of total binding in hypothalamus and cortex, respectively. Specific binding in hypothalamus and cortex was reduced by a number of drugs which are potent blockers of serotonin uptake and the binding was inhibited in a stereoselective manner by the stereoisomers of norzimelidine. In contrast, pretreatment with drugs which are weak inhibitors of serotonin uptake had no effect on specific binding. Experiments using increasing doses of [3H]CN-IMI showed that the binding in vivo was saturable. Lesioning rats with the serotonin neurotoxin 5,7-dihydroxytryptamine resulted in an 80% decrease in the specific binding in hypothalamus and a 35% decrease in cortex. The potencies of drugs to inhibit the specific binding of [3H]CN-IMI in vivo were highly correlated with their previously published potencies for inhibiting serotonin uptake in human blood platelets in vitro and for preventing the serotonin depletion induced by 4-methyl-alpha-ethyl-metatyramine in vivo. These results indicate that [3H]CN-IMI can be given to rats to provide a measure of serotonin uptake sites in the central nervous system in vivo.
mesh_terms: D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007099:Imipramine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D011335:Proadifen / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*; D013237:Stereoisomerism; D013997:Time Factors
chemical_list: C024316:cianopramine; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D011335:Proadifen; D007099:Imipramine