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 μmol/l H-5-HT. Zimelidine, trazodone, clomipramine, doxepin, and viloxazine (1 μmol/l each) enhanced the electrically-induced H overflow by 20-44%. Six other antidepressants and five neuroleptics did not increase the evoked transmitter release. Only trazodone and viloxazine also increased the H overflow in experiments in which neuronal 5-HT reuptake was already blocked by 6-nitroquipazine. 5-HT and clonidine inhibited the electrically-induced H-5-HT release by stimulation of presynaptic 5-HT autoreceptors and α-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 H-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. [ABSTRACT FROM AUTHOR]