Novel anxiolytics discriminate between postsynaptic serotonin receptors mediating different physiological responses on single neurons of the rat hippocampus

Naunyn Schmiedebergs Arch Pharmacol. 1987 Jul;336(1):5-10. doi: 10.1007/BF00177743.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Anti-Anxiety Agents / pharmacology*
  • Buspirone
  • Hippocampus / drug effects
  • Hippocampus / metabolism*
  • In Vitro Techniques
  • Male
  • Membrane Potentials / drug effects
  • Neurons / drug effects
  • Neurons / metabolism*
  • Pyramidal Tracts / drug effects
  • Pyramidal Tracts / metabolism
  • Pyrimidines / pharmacology
  • Rats
  • Receptors, Serotonin / drug effects*
  • Synapses / drug effects*
  • Synapses / metabolism
  • Tetrodotoxin / pharmacology


  • Anti-Anxiety Agents
  • Pyrimidines
  • Receptors, Serotonin
  • Tetrodotoxin
  • ipsapirone
  • gepirone
  • Buspirone