Abstract
We studied the effects of tricyclic antidepressants on the tetrabenazine (TB)-induced depletion of brain dopamine (DA) using rats. The test drugs were generally administered orally 3 hours before sacrifice and 2 mg/kg of TB or reserpine (RES) was administered subcutaneously 2 hours before sacrifice. The TB-induced DA depletion was enhanced by pretreatment with desmethylimipramine (DMI, 12.5-100 mg/kg), imipramine (12.5-100 mg/kg), chlorimipramine (25-100 mg/kg), amitriptyrine (100 mg/kg), maprotyrine (50 mg/kg) and chlorpromazine (5-20 mg/kg i.p.), while these drugs did not enhance RES-induced depletion. Observations to elucidate the action mechanism of antidepressant-induced enhancement were as follows. After TB administration, brain DA content was at the minimal level at 30 min after and on the way to recovery at 2 hours, but it approached the minimal level at 2 hours after RES administration. DMI pretreatment did not enhance the DA depletion at 0.5 hours after TB administration. In pargyline-pretreated rats, TB produced a decrease of brain DA with an increase of 3-methoxy-tyramine (3-MT), while RES showed only a slight effect on DA and 3-MT up to 2 hours. Amphetamine sulfate (20 mg/kg i.p.) slightly increased, while combinations with DMI decreased brain DA. These results suggest that tricyclic antidepressants inhibit DA reuptake from the synaptic cleft in vivo.
