Modulations of Central Serotonergic Neurotransmission by Chronic Ipsapirone in the Rat

The possible involvement of serotonin (5-HT) in both anxiety disorders and the mechanism of action of anxiolytic agents such as the benzodiazepines has been the subject of considerable research for the last twenty-five years. Nevertheless, this field remains controversial as many conflicting results exist in the literature (see Chopin and Briley, 1987). Recently, the introduction of the non-benzodiazepine anxiolytics, buspirone, gepirone and ipsapirone, which appear to act on 5-HT1A receptors, have added a new dimension to the study of 5-HT and anxiety (Traber and Glaser, 1987). Buspirone was the first of the novel anxiolytics to be shown to selectively displace the selective 5-HT1A radioligand [3H]-8-OH-DPAT from its specific sites (Gozlan et al., 1983), although further studies also demonstrated a fair affinity of buspirone for the dopamine (DA) D2 receptor (Cimino et al., 1983). The subsequent findings that ipsapirone and gepirone also bind with high affinity to 5-HT1A receptors but only with low affinity to D2 receptors (Dompert et al., 1985; Hamon et al., 1986) substantiated the working hypothesis that a serotonergic component was likely to be involved in the anxiolytic effects of these drugs. Clearly, the anxiolytic effects of these compounds do not involve an action at the benzodiazepine receptors (Taylor et al., 1985).