Enhancement by ipsapirone of dopamine release in the rat striatum

Intrastriatal administration of ipsapirone (IPSA, 0.5 and 1 mM), an agonist of 5-HT1A serotonergic receptors, enhanced in a dose-dependent manner DA release in the rat striatum, without affecting levels of the DA metabolites DOPAC and HVA. The IPSA evoked-enhancement of DA release was followed by a decrease in 5-HIAA concentration. The effects of intrastriatal administration of IPSA were mimicked by 8-OH-DPAT (0.5 mM), another agonist of 5-HT1A receptors, and were antagonized by the peripheral administration of metergoline (5 mg/kg ip) and intrastriatal administration of NAN-190 (0.5 mM). IPSA given peripherally (10 mg/kg ip) also enhanced DA release; that effect was accompanied by an increase in DOPAC and HVA levels. It is postulated that IPSA increases the release of DA from nigrostriatal terminals via activation of striatal 5-HT1A receptors in a manner independent of the activation of 5-HT1A receptors in the dorsal raphe nuclei.