The role of postsynaptic 5-HT 1A receptors in the anticonflict effect of ipsapirone

Abstract

In the present paper we have studied the anticonflict effect (in the Vogel test) of ipsapirone, a partial agonist of 5-hydroxytryptamine A (5-HT 1A) receptors, administered to the hippocampus of rats. In addition, a comparison of the effect of ipsapirone with the effect of other 5-HT 1A receptor ligands (busipone, gepirone and 8-OH-DPAT) has been carried out. Finally, the interaction between ipsapirone and NAN-190 (an antagonist of 5-HT 1A receptors and α 1-adrenoceptors) has also been examined. It has been found that ipsapirone injected intrahippocampally (i.hp.) in doses of 0.3, 1 and 3 μg (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 μg), gepirone (3–30 μg) and 8-OH-DPAT (0.3–3 μg). 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 μg) or intraperitoneally (i.p., 1 mg/kg). Futhermore, NAN-190 injected i.hp. (0.3 μg) 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 μg i.hp. or 0.5–1 mg/kg i.p.), a selective antagonist of α 1adrenoceptors. Our results seem to indicate that the anticonflict effect of ipsapirone stems from stimulation of postsynaptic 5-HT 1A receptors in the hippocampus.