Effect of nomifensine and other antidepressant drugs on acetylcholine turnover in various regions of rat brain.

Abstract

Acetylcholine (ACh) content and turnover rate (TRACh) have been measured in various brain regions of rats receiving the antidepressant nomifensine. The action of nomifensine was compared to that of amphetamine, apomorphine and several tricyclic antidepressants (amitriptyline, chlorimipramine, desipramine and iprindole). Nomifensine (14, 28 and 71 μmol/kg, i.p.) and amphetamine (27 μmol/kg, i.p.) increase TRACh in the cortex, hippocampus and diencephalon, but fail to change ACh content. Since both drugs release catecholamines, we tested the dopamine (DA) receptor agonist apomorphine (2.4 and 4.8 μmol/kg, s.c.) and found that it fails to change the TRACh or the ACh content in the cortex or diencephalon, but that it decreases TRACh in the hippocampus. Since apomorphine in doses that cause stereotypy fails to increase TRACh in cortex and hippocampus, one can infer that the increase in cortical and hippocampal TRACh caused by nomifensine and amphetamine is unrelated to their ability to cause stereotypy. Phenoxybenzamine (15 nmole) injected intraseptally fails to change hippocampal TRACh but blocks the nomifensine- and amphetamine-induced increase of TRACh in cortex and hippocampus. This indicates that the nomifensine- and amphetamine-induced increase of TRACh in the cortex and perhaps in the hippocampus is due to noradrenergic activation of the cholinergic neurons. The increase of TRACh caused by nomifensine is probably not related to its action on depression since none of the tricyclic antidepressants tested affects ACh content or TRACh in the brain regions examined. The only exception is amitriptyline, which decreases ACh content in the cortex and striatum.