196/6Z1 036tOW P antidepressant chron, i.p. 'amitriptylin_' 'imiuramin¢' 'nar_vline ' 'us vchos timulant' de sipramine nortriptyline iprindole fluoxetine neuroleptic 'haloDeridol' 'chlornromazine' 'antiserotoni_.' methysergide influence on tritium labeled mepy famine /Ro -Z- 3308/ /WB -4101 / s e rotonin LSD spipe tone dihydroalprenolol histaminergic muscarinic adrenergic dopaminergic '_' binding 'brain' cerebral-cortex corpus-striatum rat /XXVI/ /XXXI!/ /E/ Science Z10, No.4465, 88-90 /1980/ Peroutka S _ Snyder S H /Baltimore,Md.,USA/ Long-Term Antidepressant Treatrnent Decreases Spiroperidol- Labeled Serotonin Receptor Binding. The effect of long term antidepressant treatment on spiroperidol-labeled 5-HT receptor binding was investigated. Male Sprague-Dawley rats (150-J75 g) received daily i.p. .. injections of drugs fcr ZI days, allexceptpargyline(Z5mg/k# being _ivenat 10mg/kg. The frontal cerebralcortexwasusedformost binding studies. Amitriptyline, imipramine, desipramine, nortriptyl- ine, iprindole and fluox_ere competed at several neurotransmitter receptorl/ndingsites,buttheir relative potencies did not correlate with their clinical potencies. In general, the greatest potencies occurred at histamine H, receptors, labeled by 3H mepyramine, but they were also potent at muscarinic cholinergic receptors labeled by 3H quinuclidinylbenzilate. Their relative potencies at a-adrenergic receptors labeled by 3H dioxane (WB-4|01) were similar to effects at muscarinic receptors and correlated with .sedation and relief of psychomotor agitation. Z Distinct popula- tions of 5-HT receptors were labeled, with 3H 5-HT (5-HT-I) and 3H spiroperidol (5-HT-Z) respectively, 3H LSD labeling both sites to the same extent. The antidepressants were much more potent at the 5-HT-Z receptors than at the 5-HT-I receptors, effects on 3H LSD bindin_ being intermediate. The drugs were less potent at dopamine IDA) receptors labeled by 3H spiroper- idol in the corpus stricture, and at _-adrenergic receptors labeled by 3H dihydroalprenolol (DHA) than at any other receptor binding sites. Haloperidol and chlorpromazine had considerable affinities for several receptors, resembling the more active antidepressants at a-adrenergic and 5-HT-Z sites, and the most potent drugs at DA receptors. Amitriptyline, imipramine, desipramine, iprindole and pargyline reduced 3H DHA binding to _-adrenergic, and 3H spiroperidol binding to 5-HT-Z receptors, by Z0 and 40%, respectively. Desipramine reduced 3H DHA binding by Z9_0 and binding to 5-HT-Z receptors by ZI%. Binding to _-adrenergic and 5-HT receptors was unaffected by methysergide, chlorpromazine, haloperidol and fluoxitene. 3H 5-HT binding to 5-HT-I receptors decreased with imipramine and pargyline. 3H LSD binding was affected in a manner intermediate to effects on 3H spiroperidol and 3H 5-HT binding. Long-term drug treatment had no effect on muscarinic choliner- gic or a-adrenergic receptors. Neuroleptics, but not antidep- ressants, increased binding to 3H spiroperidol DA receptors in the corpus striatum. Z Tab. Z1 Ref. BJ/JB/[MS Department of Pharmacology and Experimental Therapeutics, Johns Hopkins University School of Medicine, Baltimore, Maryland Z 1Z05 U.S.A..