The Inhibitory Effect of Trifluoromethylphenylpiperazine on [ 3 H]Acetylcholine Release in Guinea Pig Hippocampal Synaptosomes Is Mediated by a 5‐Hydroxytryptamine 1 Receptor Distinct from 1A, 1B, and 1C Subtypes

The effect of the serotonergic receptor agonist 1‐( m ‐trifluoromethylphenyl)piperazine (TFMPP) was studied on the K + ‐evoked [ 3 H]acetylcholine ([ 3 H]ACh) release from guinea pig hippocampal synaptosomes loaded with [ 3 H]choline. TFMPP (5–1,000 μ M ) inhibited the evoked ACh release in a dose‐dependent manner (IC 50 = 81.8 μ M ). The inhibitory effect of TFMPP was mimicked by CGS‐12066B (10, 30, and 100 μ M ), a 5‐hydroxytryptamine 1B (5‐HT 1B )/5‐HT 1D receptor agonist; 1‐( m ‐chlorophenyl)piperazine (100 μ M ), a 5‐HT 1C /5‐HT 1B receptor agonist; and 5‐carboxamidotryptamine (10 μ M ), a nonselective 5‐HT 1 receptor agonist. 8‐Hydroxy‐2‐(di‐ n ‐propylamino)tetralin (10 and 100 μ M ), a 5‐HT 1A receptor agonist, and quipazine (10 and 100 μ M ), a 5‐HT 2 receptor agonist, did not have any significant effect. Serotonergic antagonists, such as dihydroergotamine (0.1 and 1 μ M ), metergoline (0.1 μ M ), methysergide (0.5 and 1 μ M ), or yohimbine (1 and 10 μ M ), blocked the TFMPP effect dose‐dependently. In contrast, methiotepine (0.3 and 1 μ M ), propranolol (1 μ M ), ketanserin (0.1 μ M ), mesulergine (0.1 μ M ), ICS 205930 (0.1 and 1 μ M ), and spiroperidol (1 and 7 μ M ) did not affect the TFMPP‐induced inhibition of the evoked ACh release. These data suggest that, in guinea pig hippocampus, the K + ‐evoked ACh release is modulated by a 5‐HT 1 receptor distinct from the 5‐HT 1A , 5‐HT 1B , and 5‐HT 1C subtypes.