EFFECT OF CHRONIC IPSAPIRONE TREATMENT ON THE DENSITY OF 5-HT1A RECEPTORS AND 5-HT1A RECEPTOR MESSENGER-RNA IN DISCRETE REGIONS OF THE RAT-BRAIN

There is increasing evidence that the 5-hydroxytryptamine (HT)(1A) par tial agonist ipsapirone is an effective anxiolytic/antidepressant agen t, although its mechanism of action is not clear. In this study, we in vestigated the effects of chronic ipsapirone treatment (5 or 10 mg/kg; twice daily, 3 weeks) on 5-HT1A receptor density 8-hydroxy-2-(di-n-pr opyl amino) tetralin (8OH-DPAT) binding and the level of its mRNA (in situ hybridization) in various regions of the rat (male Wistar 250 g) brain. Receptor density was reduced in the frontal cortex, but did not change significantly in the hippocampus and dorsal raphe nucleus. The level of receptor mRNA was unchanged in each of these brain regions. The present results suggest that the clinical anxiolytic effects of ip sapirone may be mediated partly by postsynaptic action on serotonergic transmission in the frontal cortex, but not in the hippocampus or dor sal raphe nuclei.