The role of postsynaptic 5-HT1A receptors in the anticonflict effect of ipsapirone

In the present paper we have studied the anticonflict effect (in the Vogel test) of ipsapirone, a partial agonist of 5-hydroxytryptamine1A (5-HT1A) receptors, administered to the hippocampus of rats. In addition, a comparison of the effect of ipsapirone with the effect of other 5-HT1A receptor ligands (busipone, gepirone and 8-OH-DPAT) has been carried out. Finally, the interaction between ipsapirone and NAN-190 (an antagonist of 5-HT1A receptors and alpha 1-adrenoceptors) has also been examined. It has been found that ipsapirone injected intrahippocampally (i.hp.) in doses of 0.3, 1 and 3 micrograms (bilaterally) shows an anticonflict effect by increasing the number of punished licks by about 36, 151 and 109%, respectively. A similar effect has also been found after i.hp. injections of buspirone (0.3-3 micrograms), gepirone (3-30 micrograms) and 8-OH-DPAT (0.3-3 micrograms). We have also demonstrated that the anticonflict effect of ipsapirone injected i.hp. is antagonized by NAN-190 administered i.hp. (0.3 or 1 microgram) or intraperitoneally (i.p., 1 mg/kg). Furthermore, NAN-190 injected i.hp. (0.3 microgram) antagonizes the anticonflict effect of ipsapirone administered i.p. (5 mg/kg). At the same time, the anticonflict effects of ipsapirone are not affected by prazosin (0.3-1 microgram i.hp. or 0.5-1 mg/kg i.p.), a selective antagonist of alpha 1-adrenoceptors. Our results seem to indicate that the anticonflict effect of ipsapirone stems from stimulation of postsynaptic 5-HT1A receptors in the hippocampus.