Chronic effects of clomipramine and clorgyline on regional levels of brain amines and acid metabolites in rats.
Chronic effects of the antidepressant drug clomipramine (CMI), a potent 5-HT uptake blocker, on regional brain amine metabolism have not been reported. Regional brain levels of dopamine, noradrenaline, 5-hydroxytryptamine (5-HT) and selected acid metabolites were measured following chronic administration (28 d via Alzet 2ML4 osmotic minipumps sc) of clorgyline (CLG, a preferential Type A monoamine oxidase inhibitor) (1 mg kg-1 per d) and CMI (5 mg kg-1 per d). Doses are expressed as HC1 salts. Male Sprague-Dawley rats (450-550 g) were used. Control animals received the distilled water vehicle. Following instant guillotine decapitation, the frontal cortex, caudate nucleus, hypothalamus and hippocampus were dissected out and stored at - 70 degrees C until assayed using high-pressure liquid chromatography with electrochemical detection. Clorgyline induced expected increases in amine levels and decreased acid metabolite levels in accord with previous studies. Clomipramine induced a decrease in 5-HIAA levels in all regions, although not as pronounced as the decrease observed with CLG. The specificity of effects of CMI for 5-HT was maintained in all brain regions except the hippocampus and frontal cortex. In these two regions CMI also induced a significant decrease in levels of DOPAC and HVA.
Mousseau
D D
DD
Department of Psychiatry, University of Alberta, Edmonton, Canada.
Greenshaw
A J
AJ
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism*; D002997:Clomipramine / Q000008:administration & dosage*; D003010:Clorgyline / Q000008:administration & dosage*; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000008:administration & dosage; D011437:Propylamines / Q000008:administration & dosage*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*
D000928:Antidepressive Agents; D002395:Catecholamines; D008996:Monoamine Oxidase Inhibitors; D011437:Propylamines; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D003010:Clorgyline; D002997:Clomipramine; D006719:Homovanillic Acid