title: Novel anxiolytics discriminate between postsynaptic serotonin receptors mediating different physiological responses on single neurons of the rat hippocampus.
abstract: The effects of buspirone on hippocampal pyramidal cells of the CA1 region were examined by means of intracellular recordings in in vitro hippocampal brain slices. Bath administration of buspirone elicited a long lasting hyperpolarization which was mediated by an increase in potassium conductance and resembled the hyperpolarizing component of the response to 5-HT (5-hydroxytryptamine). Buspirone, however, failed to mimic the depolarizing action of 5-HT or to reduce the calcium-activated after hyperpolarization. Quantitative comparisons of the hyperpolarizing responses of 5-HT and buspirone revealed that the maximal hyperpolarization induced by buspirone was significantly smaller than that induced by 5-HT. Since the buspirone induced hyperpolarization was also accompanied by a surmountable antagonism of 5-HT responses, these results indicate that buspirone behaves as a partial agonist at a subpopulation of 5-HT receptors in the CA1 region of the hippocampus. Administration of the buspirone congeners gepirone and isapirone also elicited a hyperpolarization and reduced 5-HT responses, although they lack antidopaminergic activity, indicating that the effects observed with buspirone are unlikely to be mediated through dopamine receptors. These results indicated that novel anxiolytics can discriminate between functional 5-HT receptors. In conjunction with previous biochemical and electrophysiological studies, the present results suggest that their administration might alter the balance of serotonergic actions on postsynaptic neurons.
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D002065:Buspirone; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011712:Pyramidal Tracts / Q000187:drug effects / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects*; D013569:Synapses / Q000187:drug effects* / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D014151:Anti-Anxiety Agents; D011743:Pyrimidines; D011985:Receptors, Serotonin; D013779:Tetrodotoxin; C043077:ipsapirone; C039979:gepirone; D002065:Buspirone