Evidence for a postsynaptic action of the serotonergic anxiolytics: Ipsapirone, indorenate and buspirone
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In the present experiment we analyzed whether the antianxiety action of the serotonergic 1A agonists buspirone (5 mg/kg), ipsapirone (5 mg/kg), indorenate (5 mg/kg), and 8-OH-DPAT (0.5 mg/kg) were mediated through the stimulation of pre- or postsynaptic serotonergic receptors. The experimental anxiety values were determined with the burying behavior test, where a reduction in the cumulative time of burying behavior was interpreted as a reduction in anxiety. To that purpose we analyzed the putative anxiolytic action of these drugs in animals with lesion of the serotonergic fibers after the intracerebroventricular (ICV) injection of 5,7-dihydroxytyptamine (5,7-DHT, 10 or 150 μg/10 μl). The neurochemical analysis shows that these treatments produce a statistically significant reduction in 5-HT and 5-HIAA levels in various brain areas. The results of the behavioral experiments reveal that buspirone, ipsapirone. and indorenate produced exactly the same reduction in burying behavior in lesioned animals as compared with control rats. The reduction in burying behavior produced by 8-OH-DPAT was effectively prevented by the lesion with 5,7-DHT. These data suggest that the anxiolytic effect of buspirone, ipsapirone, and indorenate is mediated via the stimulation of postsynaptic receptors, while the somatodendritic receptors are involved in the antianxiety effect of 8-OH-DPAT. © 1992.
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Anxiolytic action; Buspirone; Indorenate 8-OH-DPAT; Ipsapirone; Postsynaptic receptors 2 dipropylamino 8 hydroxytetralin; 5 hydroxyindoleacetic acid; 5,7 dihydroxytryptamine; buspirone; indorenate; ipsapirone; noradrenalin; postsynaptic receptor; serotonin; serotonin receptor; 5 hydroxyindoleacetic acid brain level; animal experiment; animal tissue; anxiety; article; behavior; controlled study; dose calculation; drug mechanism; male; nonhuman; noradrenalin brain level; priority journal; rat; serotonin brain level; serotoninergic system; synaptic transmission; tranquilizing activity; 5,7-Dihydroxytryptamine; 5-Methoxytryptamine; Animal; Anti-Anxiety Agents; Anxiety; Biogenic Monoamines; Brain Chemistry; Buspirone; Injections, Intraventricular; Male; Motor Activity; Pyrimidines; Rats; Rats, Inbred Strains; Serotonin; Stereotaxic Techniques; Support, Non-U.S. Gov't; Synapses
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