STIMULATION OF POSTSYNAPTIC 5-HT1A RECEPTORS IS RESPONSIBLE FOR THE ANTICONFLICT EFFECT OF IPSAPIRONE IN RATS

Ipsapirone (1.25 10 mg kg 1), a non-benzodiazepine anxiolytic drug with high affinity for 5-hydroxytryptamine1A (5-HT1A) receptors, increased dose-dependently the number of punished licks in the drinking conflict test (Vogel test) in rats. The anticonflict effect of the drug administered at a dose of 5 mg kg-1 was not modified in animals with lesions of 5-HT neurones, produced by p-chloroamphetamine (PCA, 2 x 10 mg kg-1). The anticonflict effect of ipsapirone in PCA-pretreated rats was antagonized by the 5-HT1A receptor and alpha-1-adrenoceptor antagonist NAN-190 (1-(2-methoxyphenyl)-4-[4-(2-phthalimmido)]butylpiperazine hydrobromide; 0.5 1 mg kg-1), but not by the selective alpha-1-adrenoceptor blocker prazosin (0.5 mg kg-1). Neither NAN-190 nor prazosin affected the punished response in PCA-pretreated rats. The present results indicate that the anticonflict effect of ipsapirone depends on stimulation of postsynaptic 5-HT1A receptors.