Effects of tricyclic antidepressants on tetrabenazine-induced depletion of brain monoamines in rats. 1. Norepinephrine.

We studied the effects of tricyclic antidepressants on the tetrabenazine (TB)-induced depletion of brain norepinephrine (NE) using rats. The test drugs were generally administered orally 3 hr before and 2 mg/kg of TB or reserpine (RES) administered subcutaneously 2 hr before sacrifice. The TB-induced NE depletion was enhanced by pretreatment with desmethylimipramine (DMI, 25--100 mg/kg), imipramine (IM, 25--100 mg/kg), chlorimipramine (100 mg/kg), maprotyrine (50 mg/kg), amitriptyrine (50--100 mg/kg), chlorpromazine (CPZ, 5--20 mg/kg i.p.,) and amphetamine sulfate (10 mg/kg). DMI partially suppressed TB-induced NE depletion at 0.5 hr after TB administration. The RES-induced NE depletion was not enhanced with these drugs except for amphetamine. DMI, IM, and CPZ suppressed it instead. DMI also enhanced the yohimbine (2 mg/kg)-induced decrease. The brain NE content showed a tendency toward recovery 2 hr after TB administration, but approached the minimal level at 0.5 hr after TB administration or at 2 hr after RES administration in non-treated rats. In pargyline-pretreated rats, TB produced a decrease of brain NE with an increase of normetanephrine, while the action of RES was weaker than that of TB, up to 2 hr. These results suggest that enhancement of the TB-induced brain NE depletion by tricyclic antidepressants reflects the blockage of NE reuptake from the synaptic cleft.