Summary
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 afterhyperpolarization. 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 anti-dopaminergic 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.
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References
Alger BE, Nicoll RA (1980) Spontaneous inhibitory post-synaptic potentials in hippocampus: Mechanism for tonic inhibition. Brain Res 200: 195–200
Andrade R, Nicoll RA (1985) The novel anxiolytic buspirone elicits a small hyperpolarization and reduces 5-HT responses at putative 5-HT1, receptors on hippocampal CA1 pyramidal cells. Abst Soc Neurosci 11: 597
Andrade R, Nicoll RA (1987) Pharmacologically distinct actions of 5-HT in CA1 region of the rat hippocampus in vitro. J Physiol (Lond) (in Press)
Bloom FE (1975) To spritz or not to spritz: the doubtful value of aimless iontophoresis. Life Sci 14: 1819–1834
Deshmukh PP, Yamamura HI, Woods L, Nelson DL (1983) Computer assisted autoradiographic localization of subtypes of serotonin receptors in rat brain. Brain Res 288: 338–343
Devivo M, Maayani S (1986) Characterization of the 5-hydroxytryptamine1A receptor-mediated inhibition of forskolin-stimulated adenylate cyclase activity in guinea-pig and rabbit hippocampal membrane. J Pharmacol Exp Ther 238: 248–253
Engel JA, Hjorth S, Svensson K, Carlsson A, Liljequist S (1984) Anticonflict effect of the putative serotonin receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). Eur J Pharmacol 105: 365–368
Gelbach G, Vandermaelen CP (1985) The nonbenzodiazepine anti-depressant anxiolytic candidate, gepirone, inhibits serotonergic dorsal raphé neurons in the rat brain slice. Abst Soc Neurosci 11: 186
Glaser T, Traber J (1983) Buspirone: actions on serotonin receptors in calf hippocampus. Eur J Pharmacol 88: 137–138
Glaser T, Traber J (1985) Binding of the putative anxiolytic TVX Q 7821 to hippocampal 5-hydroxytryptamine (5-HT) recognition sites. Naunyn-Schmiedeberg's Arch Pharmacol 329: 211–215
Goldberg HL, Finnerty RJ (1979) The comparative efficacy of buspirone and diazepam in the treatment of anxiety. Am J Psychiat 136: 1184–1187
Hjorth S, Carlsson A (1982) Buspirone: effects on central monoaminergic transmission-possible relevance to animal experimental and clinical findings. Eur J Pharmacol 83: 299–303
Kenakin TP, Black JW (1978) The pharmacological classification of practolol and chloropractolol. Mol Pharmacol 14: 607–623
McMillen BA, Mattiace LA (1983) Comparative neuropharmacology of buspirone and MJ-13805, a potential anti-anxiety drug. J Neural Transm 7: 255–265
Nicoll RA, Alger BE (1981) A simple chamber for recording from submerged brain slices. J Neurosci Meth 4: 153–156
Pazos A, Palacios JM (1985) Quantitative autoradiographic mapping of serotonin receptors in the rat brain. I. Serotonin-1 receptors. Brain Res 346: 205–230
Peroutka SJ (1985) Selective labelling of 5-HT1A and 5-HT1B binding sites in bovine brain. Brain Res 344: 167–171
Riblet LA, Taylor DP, Eison MS, Stanton HC (1982) Pharmacology and neurochemistry of buspirone. J Clin Psychiat 43: 11–16
Rowan MJ, Anwyl R (1987) Neurophysiological effects of buspirone and isapirone in the hippocampus: comparison with 5-hydroxytryptamine. Eur J Pharmacol 132: 93–96
Sprouse JS, Aghajanian GK (1987) Electrophysiological responses of serotonergic dorsal raphe neurons to 5-HT1A and 5-HT1B agonists. Synapse 1: 3–9
Taylor DP, Allen LE, Becker JE, Crane M, Hyslop DK, Riblet LA (1984) Changing concepts for the biochemical action of the anxioselective drug, buspirone. Drug Dev Res 4: 95–108
Traber J, Davies MA, Dompert WU, Glaset T, Schuurman T, Seidel PR (1984) Brain serotonin receptors as target for the putative anxiolytic TVX Q 7821. Brain Res Bull 12: 741–744
Temple DL, Yevich JP, New JS (1982) Buspirone: Chemical profile of a new class of anxioselective agents. J Clin Psychiat 43: 4–9
VanderMaelen CP, Matheson GK, Wilderman RC, Patterson LA (1986) Inhibition of serotonergic dorsal raphé neurons by systemic and iontophoretic administration of buspirone, a non-benzodiazepine anxiolytic drug. Eur J Pharmacol 129: 123–130
Vogel JR, Beer B, Clody DE (1971) A simple and reliable conflict procedure for testing anti-anxiety agents. Psychopharmacology 21: 1–7
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Andrade, R., Nicoll, R.A. Novel anxiolytics discriminate between postsynaptic serotonin receptors mediating different physiological responses on single neurons of the rat hippocampus. Naunyn-Schmiedeberg's Arch Pharmacol 336, 5–10 (1987). https://doi.org/10.1007/BF00177743
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DOI: https://doi.org/10.1007/BF00177743