Abstract
Early electrophysiological experiments on the dorsal raphe (DR) nucleus using extracellular unit recording showed a slow continuous firing rate of 0.5-3 Hz, which could be inhibited by systemic administration of the potent hallucinogen lysergic acid diethylamide (LSD; Aghajanian et al., 1968). The effects of LSD were assumed to be mediated via 5-hydroxytryptamine (5-HT) receptors. To determine the role of tonic 5-HT release on DR neuronal excitability, animals were pre-treated with the specific 5-HT synthesis inhibitor p-chlorophenylalanine (p-CPA). However, when given alone, p-CPA did not appreciably alter DR neuronal firing rate (Aghajanian et al., 1970). On the other hand, monoamine oxidase inhibitors caused a marked decrease in base-line firing rates, suggesting that negative feedback was due to an extracellular accumulation of 5-HT; pre-treatment with p-CPA almost totally prevented the inhibitory effect of monamine oxidase inhibitors, but it had no effect on the LSD-mediated reduction in firing. This confirmed the earlier suggestion that LSD must act at a point distal to 5-HT release.
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References
Aghajanian, G. K. (1985). Modulation of a transient outward current in serotonergic neurones by α1-adrenoceptors. Nature, 315, 501–503
Aghajanian, G. K. and VanderMaelen, C. P. (1982a). Intracellular recordings from serotoninergic dorsal raphe neurons: pacemaker potentials and the effect of LSD. Brain Res., 238, 463–469
Aghajanian, G. K. and VanderMaelen, C. P. (1982b). Intracellular identification of central noradrenergic and serotonergic neurones by a new double labelling procedure. J. Neurosci., 2, 1786–1792.
Aghajanian, G. K., Foote, W. E. and Sheard, M. H. (1968). Lysergic acid diethylamide: sensitive neuronal units in the midbrain raphe. Science, 161, 706–708
Aghajanian, G. K., Graham, A. W. and Sheard, M. H. (1970). Serotonin-containing neurons in brain: depression of firing by monoamine oxidase inhibitors. Science, 189, 1100–1102
Aghajanian, G. K., Kuhar, M. J. and Roth, R. H. (1973). Serotonin-containing neuronal perikarya and terminals: differential effects of p-chlorophenylalanine. Brain Res., 54, 85–101
Andrade, R., Malenka, R. C. and Nicoll, R. A. (1986). A G protein couples serotonin and GABAB receptors to the same channels in hippocampus. Science, 234, 1261–1265
Chazal, G. and Ralston, III, H. J. (1987). Serotonin-containing structures in the nucleus raphe dorsalis of the cat: an ultrastructural analysis of dendrites, presynaptic dendrites, and axon terminals. J. Comp. Neurol., 259, 317–329
Colino, A. and Halliwell, J. V. (1986). 8-OH-DPAT is a strong antagonist of 5-HT action in rat hippocampus. Eur. J. Pharmacol., 130, 151–152
Crunelli, V., Forda, S., Brooks, P. A., Wilson, K. C. P., Wise, J. C. M. and Kelly, J. S. (1983). Passive membrane properties of neurones in the dorsal raphe and periaqueductal grey recorded in vitro. Neurosci. Lett., 40, 263–268
Gallagher, D. W. and Aghajanian, G. K. (1976). Inhibition of firing of raphe neurones by tryptophan and 5-hydroxytryptophan: blockade by inhibiting serotonin synthesis with RO-4–4602. Neuropharmacology, 15, 149–156
Lakoski, J. M. and Aghajanian, G. K. (1985). Effects of ketanserin on neuronal responses to serotonin in the prefrontal cortex, lateral geniculate and dorsal raphe nucleus. Neuropharmacology, 24, 265–273
Martin, L. L. and Sanders-Bush, E. (1982). Comparison of the pharmacological characteristics of 5-HT1 and 5-HT2 binding sites with those of serotonin autoreceptors which modulate serotonin release. Naunyn-Schmiedeberg’s Arch. Pharmacol., 321, 165–170
Maura, G., Roccatagliata, E. and Raiteri, M. (1986). Serotonin autoreceptor in rat hippocampus: pharmacological characterization as a subtype of the 5-HT1receptor. Naunyn-Schmiedeberg’s Arch. Pharmacol., 334, 323–326
Middlemiss, D. N. and Fozard, J. R. (1983). 8-hydroxy-2-(di-n-propylamino)tetralin discriminates between subtypes of the 5-HT1 recognition site. Eur. J. Pharmacol., 90, 151–153
Mosko, S. S. and Jacobs, B. L. (1976). Recording of dorsal raphe unit activity in vitro. Neurosci. Lett., 2, 195–200
Mosko, S. S. and Jacobs, B. L. (1977). Electrophysiological evidence against negative neuronal feedback from the forebrain controlling midbrain raphe unit activity. Brain Res., 119, 291–303
Penington, N. J., Rainnie, D. G. and Kelly, J. S. (1987a). Intracellular studies of rat dorsal raphe neurones in vitro. Neurosci. Lett., Suppl. 29, S17
Penington, N. J., Rainnie, D. G. and Kelly, J. S. (1987b). Studies on the pacemaker potentials of rat dorsal raphe neurones in vitro. Proc. Intl. Union Pharmacol., X, P260
Rainnie, D. G., Penington, N. J. and Kelly, J. S. (1987a). On the hyperpolarising action of 5-hydroxytryptamine on rat dorsal raphe neurones in vitro. Neurosci. Lett., Suppl. 29, S72
Rainnie, D. G., Penington, N. J. and Kelly, J. S. (1987b). Activation of ‘A’ currents in dorsal raphe neurones in vitro. Neuroscience, 22, Suppl., S696, Abst. 2078P
Sheard, M. H., Zolovick, A. and Aghajanian, G. K. (1972). Raphe neurons: effect of tricylic antidepressant drugs. Brain Res., 43, 690–94
Sprouse, J. S. and Aghajanian, G. K. (1986). (−)-Propranolol blocks the inhibition of serotonergic dorsal raphe cell firing by 5-HT1A selective agonists. Eur. J. Pharmacol., 128, 295–298
Sprouse, J. S. and Aghajanian, G. K. (1987). Electrophysiological responses of serotoninergic dorsal raphe neurons to 5-HT1A and 5-HT1B agonists. Synapse, 1, 3–9
Verge, D., Daval, G., Patey, A., Gozlan, H., El Mestikawy, S. and Hamon, M. (1985). Presynaptic 5-HT autoreceptors on serotonergic cell bodies and/or dendrites but not terminals are of the 5-HT1A subtype. Eur. J. Pharmacol., 113, 463–464
Wang, R. Y. and Aghajanian, G. K. (1977). Antidromically identified serotonergic neurons in the rat midbrain raphe: evidence for collateral inhibition. Brain Res., 132, 186–193
Yoshimura, M. and Higashi, H. (1985). 5-hydroxytryptamine mediates inhibitory postsynaptic potentials in rat dorsal raphe neurones. Neurosci. Lett., 53, 69–74
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Kelly, J.S., Penington, N.J., Rainnie, D.G. (1989). Need the Autoregulation of Raphe Neurones Involve 5-Hydroxytryptamine?. In: Mylecharane, E.J., Angus, J.A., de la Lande, I.S., Humphrey, P.P.A. (eds) Serotonin. Satellite Symposia of the IUPHAR 10th International Congress of Pharmacology. Palgrave Macmillan, London. https://doi.org/10.1007/978-1-349-10114-6_8
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