Effect of antidepressant and neuroleptic drugs on the electrically evoked release of serotonin from rat cerebral cortex

The effect of antidepressant and neuroleptic drugs on the electrically evoked release of serotonin (5-HT) was investigated in rat brain cortical slices preincubated with 0.1 mol/l ³H-5-HT. Zimelidine, trazodone, clomipramine, doxepin, and viloxazine (1 mol/l each) enhanced the electrically-induced ³H overflow by 20–44%. Six other antidepressants and five neuroleptics did not increase the evoked transmitter release. Only trazodone and viloxazine also increased the ³H overflow in experiments in which neuronal 5-HT reuptake was already blocked by 6-nitroquipazine. 5-HT and clonidine inhibited the electrically-induced ³H-5-HT release by stimulation of presynaptic 5-HT autoreceptors and ₂-adrenoceptors, respectively; trazodone and viloxazine had no effect on the concentration-response curves of 5-HT and clonidine. Other psychotropic agents with well known antiserotonergic activities also failed to block presynaptic 5-HT autoreceptors. It is concluded that zimelidine, clomipramine, and doxepin enhanced the ³H-5-HT overflow by inhibition of neuronal 5-HT uptake, whereas the increase produced by trazodone and viloxazine cannot be explained by reuptake inhibition or interaction with presynaptic receptors.