NEURONAL CIRCUITS INVOLVED IN THE ANXIOLYTIC EFFECTS OF THE 5-HT1A RECEPTOR AGONISTS 8-OH-DPAT, IPSAPIRONE AND BUSPIRONE IN THE RAT

In rats, the 5-HT1A receptor full agonist 8-hydroxy-2-(di-n-propylamin o)tetralin (8-OH-DPAT) and the 5-HT1A receptor partial agonists ipsapi rone and buspirone dose dependently and completely inhibited shock-ind uced ultrasonic vocalization after systemic injection and after microi njection into the dorsal raphe nucleus, a brain region rich in somatod endritic 5-HT1A receptors. As compared with injection into the dorsal raphe nucleus, ipsapirone and 8-OH-DPAT were significantly less potent after microinjection into the lateral ventricle or the median raphe n ucleus. Depletion of brain 5-HT (5-hydroxytryptamine) by means of 5,7- dihydroxytryptamine or parachlorophenylalanine inhibited ultrasonic vo calization. In lesioned rats, however, ipsapirone (i.p. or dorsal raph e nucleus) and 8-OH-DPAT (dorsal raphe nucleus) retained their ability to inhibit ultrasonic vocalization and, in nonlesioned rats, bilatera l injection of ipsapirone, buspirone and 8-OH-DPAT into the dorsal hip pocampus and the amygdala - two brain regions rich in postsynaptic 5-H T1A receptors - also inhibited ultrasonic vocalization. In a Geller-Se ifter conflict test, i.p. and local injection of 8-OH-DPAT in the dors al raphe nucleus and the hippocampus selectively enhanced punished res ponding. It is suggested that both presynaptic and (possibly to a less er extent) postsynaptic 5-HT1A receptors are involved in the anxiolyti c effects of ipsapirone, buspirone, and 8-OH-DPAT.