EVIDENCE FOR THE INVOLVEMENT OF 5-HT1A RECEPTORS IN THE ANTICONFLICT EFFECT OF IPSAPIRONE IN RATS

The anticonflict activity of ipsapirone, a non-benzodiazepine anxiolytic drug, with high affinity for 5-hydroxytryptamine1A (5-HT1A) receptors, was studied in the drinking conflict test in the rat. The drug, administered in doses 1.25-20 mg/kg increased the number of punished licks, with the maximum effect observed after doses of 5-20 mg/kg of ipsapirone. The anticonflict effect of ipsapirone (5 mg/kg) was dose-dependently antagonized by the 5-HT1A receptor, alpha-1-adrenoceptor and dopamine receptor antagonist, NAN-190 (0.25-1 mg/kg) and by the beta-adrenoceptor blocker, SDZ 21009, which also has a high affinity for 5-HT1A and 5-HT1B receptors (2-8 mg/kg). On the other hand, the non-selective 5-HT receptor antagonist, metergoline (2 and 4 mg/kg), the 5-HT2/5-HT1C receptor antagonist, ritanserin (0.25 and 0.5 mg/kg), the selective alpha-1-adrenoceptor blocker, prazosin (0.25-0.5 mg/kg) and the beta-blockers, betaxolol (8 mg/kg) and ICI 118 551 (8 mg/kg), which have no affinity for 5-HT receptors, did not affect the anticonflict action of ipsapirone. The effect of ipsapirone was also not modified in animals with lesions of 5-HT neurones, produced by p-chloroamphetamine (PCA-2 x 10 mg/kg). These results suggest that the anticonflict effect of ipsapirone in the Vogel test, results from its interaction with 5-HT1A receptors, which are probably located postsynaptically.