Anxiolytic effect of the 5-HT1A compounds 8-hydroxy-2-(di-n-propylamino) tetralin and ipsapirone in the social interaction paradigm: evidence of a presynaptic action.

This study analyses at which site, pre- or postsynaptic, the 5-HT1A ligands--8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and ipsapirone--induce their anxiolytic action. The experimental anxiety was assessed in the social interaction test. An anxiolytic action was observed after the systemic administration of 8-OH-DPAT (0.25 and 0.5 mg/kg) and ipsapirone (5 but not 10 mg/kg). In 5,7-dihydroxytryptamine (5,7-DHT, 150 micrograms/10 microliters) lesioned rats the anxiolytic effect of 8-OH-DPAT and ipsapirone was not observed, suggesting a presynaptic action of these drugs. When directly injected into the dorsal raphe nucleus 8-OH-DPAT (0.1 microgram/microliter) and ipsapirone (0.2 microgram/microliter), both compounds produce anxiolytic effects. At same doses, these drugs lacked an effect after their intrahippocampal infusion. All data strongly suggest that both drugs act presynaptically to reduce the anxiety levels in the social interaction paradigm.