Effect of antidepressants on glutamatergic autoregulatory presynaptic mechanism in the rat cerebral cortex

: Amitriptyline, imipramine, desipramine, viloxazine, moclobemide and its derivative, novel antidepressant befol (10(-6)-5 x 10(-4) M) decreased by 12-20% K(+)-stimulated 3H-D-asp release from perfused synaptosomes of rat brain cortex. Glutamic acid diethyl ester (GDEE) (10(-4) M) antagonized the effect of amitriptyline, imipramine, desipramine and befol and reversed the effect of moclobemide and viloxazine. Among neuroleptics studied, only carbidine, which possesses antidepressant activity together with antipsychotic one in clinics, decreased 3H-D-asp release by GDEE-sensitive mechanism. Effect of haloperidol and chlorpromazine was not affected by GDEE. It is concluded that autoregulatory mechanism on the terminals of glutamatergic neurons may be involved in the antidepressant action.