Differential properties of pre- and postsynaptic 5-hydroxytryptamine1A receptors in the dorsal raphe and hippocampus: I. Effect of spiperone.

The i.v. administration of the 5-hydroxytryptamine (5-HT)1A antagonist spiperone (1 mg/kg) antagonized the suppressant effect of microiontophoretic applications of 5-HT and of the selective 5-HT1A agonist 8-OH-DPAT on the firing activity of the rat dorsal raphe 5-HT neurons. In contrast, the same dose of spiperone did not alter the responsiveness to microiontophoretic applications of 5-HT and 8-OH-DPAT of pyramidal neurons in the CA3 region of the hippocampus, therefore indicating that spiperone does not act as a classical antagonist at these postsynaptic 5-HT1A receptors. After two daily injections of spiperone (5 mg/kg, i.p.) and a third one immediately before the experiment, the responsiveness of CA3 pyramidal neurons to 5-HT applied by microiontophoresis and to that released by the electrical stimulation of the ascending 5-HT pathway was markedly reduced. After 24, but not 12 or 48 h after a single injection of spiperone (5 mg/kg, i.p.), the responsiveness to exogenous and endogenous 5-HT was decreased. Smaller doses (1 and 2.5 mg/kg, i.p.) were ineffective. Haloperidol and ketanserin (5 mg/kg, i.p., 24 h before the experiment) were ineffective in blocking the responsiveness of CA3 pyramidal neurons to 5-HT, thereby demonstrating that the dopamine D2 and 5-HT2 properties of spiperone could not account for the attenuated responsiveness of the hippocampus neurons to 5-HT. Methiothepin (5 mg/kg, i.p., 24 h before recording), as for spiperone, antagonized the suppressant effect of 5-HT applied by microiontophoresis.(ABSTRACT TRUNCATED AT 250 WORDS)