Antagonism by antidepressant drugs of the inhibitory effect of trifluoromethylphenylpiperazine (TFMPP) on [3H]acetylcholine release in rat or guinea-pig hippocampal synaptosomes

The effects of antidepressant drugs on the m-trifluoromethylphenylpiperazine (TFMPP)-induced inhibition of K+-evoked [3H]acetylcholine (3H-ACh) release were studied in rat or guinea-pig hippocampal synaptosomes. The serotonergic agonist TFMPP dose-dependently inhibited the K+-evoked release of 3H-ACh in rat hippocampus (IC50=53 μM). Chlorimipramine (5–500 nM), a typical tricyclic antidepressant, and minaprine (1–100 nM), an atypical antidepressant drug, partially antagonized the effect of TFMPP on 3H-ACh release in a dose-dependent manner. Other antidepressants (imipramine, citalopram, indalpine, fluoxetine, fluvoxamine, oxaprotiline, mianserine, nomifensine), at concentrations ranging from 10 to 500 nM, produced similar effects. Drugs with no antidepressant effect, such as chlorpromazine, clobazam, and cocaine (50, 100 and 500 nM), were without significant influence on the TFMPP effect. In guinea-pig hippocampal synaptosomes, minaprine (50 nM) also reduced the TFMPP-induced inhibition of 3H-ACh release, whilst clobazam (50 nM) was inactive. These results suggest that antidepressant drugs interact in vitro with heterologous serotonergic presynaptic receptors on cholinergic nerve terminals in rat and guinea-pig hippocampus.