ARE POSTSYNAPTIC 5-HT1A RECEPTORS INVOLVED IN THE ANXIOLYTIC EFFECTS OF 5-HT1A RECEPTOR AGONISTS AND IN THEIR INHIBITORY EFFECTS ON THE FIRING OF SEROTONERGIC NEURONS IN THE RAT

Previous studies have shown that injection of 5-hydroxytryptamine (ser otonin) receptor agonists in the dorsal raphe nucleus (DRN) to stimula te somatodendritic 5-HT1A autoreceptors or in the hippocampus to stimu late postsynaptic 5-HT1A receptors, induces anxiolytic-like effects in the rat. The mechanisms triggered by the latter treatment were invest igated by measuring both the electrical activity of serotonergic DRN n eurons and the anxiolytic response in rats receiving injections with 8 -hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) or ipsapirone into the dorsal hippocampus. Anxiety-related behavior was estimated by reco rding the time of ultrasonic vocalization (USV) due to electric foot s hocks under standardized conditions. Intrahippocampal application of 8 -OH-DPAT or ipsapirone produced a dose-dependent inhibition of the fir ing of serotonergic DRN neurons and of the shock-induced USV response. However, the range of efficient doses of 8-OH-DPAT via the intrahippo campal route (1-10 mu g/rat) was larger than that using the i.v. route of injection (0.15-2.5 mu g/rat). Furthermore, maximal inhibition of the firing of DRN serotonergic neurons occurred earlier when 8-OH-DPAT was injected i.v. (within 1-2 min) than when it was injected into the dorsal hippocampus (within 5 min). Interestingly, the injection of 8- OH-DPAT into the striatum, where 5-HT1A receptors are hardly detectabl e, or a lateral ventricle, also yielded dose-dependent reduction in bo th the firing rate of serotonergic DRN neurons and the USV response. F inally, local lesion with ibotenic acid to eliminate postsynaptic 5-HT 1A receptors did not alter the inhibitory effects of intrahippocampal application of 8-OH-DPAT on the firing of serotonergic DRN neurons and the USV response. These data indicated that postsynaptic 5-HT1A recep tors were not responsible for the inhibitory effects of 8-OH-DPAT and ipsapirone injected in forebrain areas on the electrical activity of s erotonergic neurons and the USV response in rats. As shown by the auto radiographic labeling by [H-3]8-OH-DPAT at distance from its injection site in the dorsal hippocampus, the diffusion of 5-HT1A receptor agon ists (from injected areas in the forebrain to the DRN where they direc tly inhibit the electrical activity of serotonergic neurons) more like ly accounted for their anxiolytic-like effects.