In vivo effects of benztropine and nomifensine on dopamine and noradrenaline terminals in rat brain

6-Hydroxydopamine (6-OHDA) was given intracerebroventricularly, 200 μg to rats with weight 200–250 g. After 14 days dopamine was measured in the corpus striatum and noradrenaline in the rest of the forebrain. Dopamine decreased to 46% and noradrenaline to 23% of the control values. 4 different drugs, benztropine (1, 5 and 25 mg/kg), nomifensine (10 mg/kg), desipramine (25 mg/kg) and amphetamine (5 mg/kg) were given i.p. 30 min before or 15 min after the 6-OHDA to see if they could prevent the depletion of dopamine and nor-adrenaline. Nomifensine, desipramine and, to a lesser degree, amphetamine prevented the depletion of noradrenaline when given before 6-OHDA, and nomifensine also had some effect when given after 6-OHDA. Nomifensine and amphetamine had an effect on the dopamine content when given both before and after 6-OHDA. Desipramine had no effect on dopamine. The largest dose of benztropine had a small effect on dopamine when given after but not when given before 6-OHDA.The results may in an indirect way give some information about the in vivo action of the drugs on the release and uptake of catecholamines in the brain. Thus it is concluded that amphetamine, desipramine and nomifensine all had an effect on the uptake mechanism in noradrenergic terminals and that in addition nomifensine had a releasing effect on these terminals. Amphetamine and nomifensine but not desipramine both inhibited uptake and provoked the release of dopamine in the dopaminergic terminals. The releasing effect of benztropine on the dopamine terminals may have been too small to have clinical relevance.