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.