Chronic effects of clomipramine and clorgyline on regional levels of brain amines and acid metabolites in rats

Abstract

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⁻¹per d) and CMI (5mg kg⁻¹per d). Doses are expressed as HCl 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 °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.