Effects of tricyclic antidepressants on the content and metabolism of dopamine in the rat striatum.

The effects of tricyclic antidepressants: imipramine (IMI), desmethylimipramine (DMI), and amitriptyline (AMI) on the levels and metabolism of dopamine (DA) in rat striatum were investigated. All three antidepressant drugs produced at 60 min a marked increase in striatal DA content. The DA-enhancing effect of DMI was dose dependent until a ceiling (about 140% increase) was reached. The time-course study of DMI (10 mg/kg) revealed a biphasic effect: an initial accumulation of DA peaking at 60 min followed by a decline in levels to about 20% of controls at 3 h after administration. In DMI-treated rats, homovanilic acid concentration was decreased to 58% at 60 min, but increased to 118% at 3 h, whereas 3,4-dihydroxyphenylacetic acid levels were unchanged at 60 min, but significantly suppressed at 3-h time interval. The observed effects of tricyclic anti-depressants on striatal DA may be relevant to the beneficial effect of these compounds in Parkinson's disease.