Cholinergic Excitation of A9 and A10 Dopaminergic Neurones in Vitro through Both Nicotinic and Muscarinic Receptors

  • M. G. Lacey
  • P. Calabresi
  • R. A. North
Part of the Advances in Behavioral Biology book series (ABBI, volume 39)


There are no cholinergic neurones within either substantia nigra (A9) or ventral tegmental (A10) area (Mesulam et al., 1983). However choline acetyltransferase-immunoreactive terminals within substantia nigra pars compacta have been observed (Beninato & Spencer, 1988). Such innervation may arise from the cholinergic neurones of the pedunculopontine nucleus (PPN) (Woolfe & Butcher, 1986; Clarke et al., 1987; but see Lee et al., 1988).


Muscarinic Receptor Voltage Clamp Pedunculopontine Nucleus Neuronal Nicotinic Receptor Nicotinic Response 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Beninato, M. & Spencer, R.F. 1988. The cholinergic innervation of the rat substantia nigra: a light and electron microscopic immunohistochemical study. Exp. Brain Res. 72: 178–184.PubMedCrossRefGoogle Scholar
  2. Benham, C.D., Bolton, T.B. & Lang, R.J. 1985. Acetylcholine activates an inward current in single mammalian smooth muscle cells. Nature 316: 345–347.PubMedCrossRefGoogle Scholar
  3. Berridge, M.J. 1987. Inositol triphosphate and diacylglycerol: two interacting second messengers. Ann. Rev. Biochem. 56: 159–193.PubMedCrossRefGoogle Scholar
  4. Bolton, T.B. & Lim, S.P. 1989. Properties of calcium stores and transient outward currents in single smooth muscle cells of rabbit intestine. J. Physiol. 409: 385–402.PubMedGoogle Scholar
  5. Brown, D.A. & Adams, P.R. 1980. Muscarinic suppression of a novel voltage-sensitive Kb-current in a vertebrate neurone. Nature 283: 673–676PubMedCrossRefGoogle Scholar
  6. Calabresi, P., Lacey, M.C. & North, R.A. 1989. Nicotinic excitation of rat ventral tegmental neurones in vitro studied by intracellular recording. Brit. J. Pharmacol. 98: 135–140.Google Scholar
  7. Chiappinelli, V.A. 1983. Kappa-bungarotoxin: a probe for the neuronal nicotinic receptor in the avian ciliary ganglion. Brain Res. 277: 9–21.PubMedCrossRefGoogle Scholar
  8. Christie, M.J. & North, R.A. 1988. Control of ion conductances by muscarinic receptors. Trends Pharmacol. Sci. Subtypes of Muscarinic Receptors III: 30–34.Google Scholar
  9. Clarke, P.B.S. & Pert, A. 1985. Autoradiographic evidence for nicotinic receptors on nigrostriatal and mesolimbic dopaminergic neurons. Brain Res. 348: 355–358.PubMedCrossRefGoogle Scholar
  10. Clarke, P.B.S., Pert, A., Hommer, D.W. & Skirboll, L.R. 1985. Electrophysiological actions of nicotine on substantia nigra single units. Brit. J. Pharmacol. 85: 327–835.Google Scholar
  11. Clarke, P.B.S., Hommer, D.W., Pert, A. & Skirboll, L.R. 1987. Innervation of substantia nigra neurons by cholinergic afferents from pedunculopontine nucleus in the rat: neuroanatomical and electrophysiological evidence. Neurosci. 23: 1011–1019.CrossRefGoogle Scholar
  12. Cross, A.J. & Waddington, J.L. 1980. [3H]quinuclidinyl benzylate and [3H]GABA receptor binding in rat substantia nigra after 6-hydroxydopamine lesions. Neurosci. Lett. 17: 271–275.PubMedCrossRefGoogle Scholar
  13. De Belleroche, J. & Gardner, I.M. 1985. Muscarinic receptors discriminated by pirenzepine are involved in the regulation of neurotransmitter release in rat nucleus accumbens. Br. J Pharmac. 86: 505–508.Google Scholar
  14. Duvoisin, R.M., Deneris, E.S., Patrick, J. & Heinemann, S. 1989. The functional diversity of the neuronal nicotinic acetylcholine receptors is increased by a novel subunit: 04. Neuron 3: 457–496.CrossRefGoogle Scholar
  15. Egan, T.M. & North, R.A. 1986. Actions of acetylcholine and nicotine on rat locus coeruleus neurones in vitro. Neuroscience 19: 565–571.PubMedCrossRefGoogle Scholar
  16. Fibiger, H.C. & Phillips, A.G. 1986. Reward, motivation, cognition: psychobiology of mesotelencephalic dopamine systems. In: Handbook of Physiology section 1. Vol. IV, pp. 647–676. American Physiological Society, Bethesda, USA.Google Scholar
  17. Gil, D.W. & Wolfe, B.B. 1985. Pirenzepine distinguishes between muscarinic receptor-mediated phosphoinositide breakdown and inhibition of adenylate cyclase. J. Pharmac. Exp. Ther. 232: 608–616.Google Scholar
  18. Giorguieff, M.F., Le Floc’h, M.L., Glowinski, J. & Besson, M.J. 1977. Involvement of cholinergic presynaptic receptors of nicotinic and muscarinic types in the control of the spontaneous release of dopamine from striatal dopaminergic terminals in the rat. J. Pharmac. Exp. Ther. 200, 535–544.Google Scholar
  19. Grenhoff, J., Aston-Jones, G. & Svensson, T.H. 1986. Nicotinic effects on the firing pattern of midbrain dopamine neurons. Acta Physiol. Scand. 128: 351–358.PubMedCrossRefGoogle Scholar
  20. Hammer, R., Berrie, C.P., Birdsall, N.M.J., Burgen, A.S.V. & Hulme, E.C. 1980. Pirenzepine distinguishes between different subclasses of muscarinic receptors. Nature 283: 90–92.PubMedCrossRefGoogle Scholar
  21. Lacey, M.G., Mercuri, N.B. & North, R.A. 1987. Dopamine acts on D2 receptors to increase potassium conductance in neurones of the rat substantia nigra zona compacta. J. Physiol. 392: 397–416.PubMedGoogle Scholar
  22. Lacey, M.C., Mercuri, N.B. & North, R.A. 1989. Two cell types in the rat substantia nigra zona compacta distinguished by membrane properties and the actions of dopamine and opioids. J. Neurosci. 9: 1233–1241.PubMedGoogle Scholar
  23. Lacey, M.C., Calabresi, P. & North, R.A. 1990. Muscarine depolarizes rat substantia nigra zona compacta and ventral tegmental neurons in vitro through Ml receptors. J. Pharmacol. Exp. Ther. (in press).Google Scholar
  24. Lee, H.L., Rye, D.B., Hallanger, A., Levey, A.I. & Wainer, B.H. 1988. Cholinergic vs. noncholinergic efferents from the mesopontine tegmentum to the extrapyramidal motor system. J.Comp. Neurol. 275: 469–492.PubMedCrossRefGoogle Scholar
  25. Lichtensteiger, W., Hefti, F., Felix, D., Huwyler, T., Melamed, E. & Schlumpf, M. 1982. Stimulation of nigrostriatal dopamine neurones by nicotine. Neuropharmacol. 21: 963–968.CrossRefGoogle Scholar
  26. Loring, R.H. & Zigmond, R.E. 1988. Characterization of neuronal nicotinic receptors by snake venom neurotoxins Trends Neurosci. 11: 73–78.PubMedCrossRefGoogle Scholar
  27. Madison, D.V., Lancaster, B. & Nicoll, R.A. 1987. Voltage clamp analysis of cholinergic action in the hippocampus. J. Neurosci. 7: 733–741.PubMedGoogle Scholar
  28. McCormick, D.A. & Prince, D.A. 1987. Acetylcholine causes rapid excitation in the medial habenular nucleus of guinea pig. in vitro. J. Neurosci. 7: 742–752.PubMedGoogle Scholar
  29. Mesulam, M.-M., Mufson, E.J., Wainer, B.H. & Level, A.I. 1983. Central cholinergic pathways in the rat: an overview based on an alternative nomenclature (Chl-Ch6). Neurosci. 10: 1185–1201.CrossRefGoogle Scholar
  30. Niijima, K. & Yoshida, M. 1988. Activation of mesencephalic dopamine neurons by chemical stimulation of the nucleus tegmenti pedunculopontinus pars compacta. Brain Res. 451, 163–171.PubMedCrossRefGoogle Scholar
  31. Nonoka, R. & Moroji, T. 1984. Quantitative autoradiography of muscarinic cholinergic receptors in the rat brain. Brain Res. 296: 295–303.CrossRefGoogle Scholar
  32. North, R.A. & Tokimasa, T. 1983. Depression of calcium-dependent potassium conductance of guinea-pig myenteric neurones by muscarinic agonists. J. Physiol. 342: 253–266.PubMedGoogle Scholar
  33. North, R.A., Slack, B.E. & Surprenant, A. 1985. Muscarinic MI and M2 receptors mediate depolarization and presynaptic inhibition in guinea pig enteric nervous system. J. Physiol. 368: 435–452.PubMedGoogle Scholar
  34. Peralta, E.G., Ashkenazi, A., Winslow, J.W. Ramachandran, J. & Capon, D.J. 1988. Differential regulation of PI hydrolysis and adenyl cyclase by muscarinic receptor subtypes. Nature 334: 434–437.PubMedCrossRefGoogle Scholar
  35. Rang, H.P. 1982. The action of ganglionic blocking drugs on the synaptic responses of rat submandibular ganglion cells. Br. J. Pharmacol. 75, 151–168.PubMedGoogle Scholar
  36. Scarnati, E., Proia, A., Campana, E. & Pacitti, C. 1986. A microiontophoretic study on the nature of the putative synaptic neurotransmitter involved in the pedunculopontinesubstantia nigra pars compacta excitatory pathway of the rat. Exp. Brain Res. 62: 470–478.PubMedCrossRefGoogle Scholar
  37. Schulz, D.W. & Zigmond, R.E. 1989. Neuronal bungarotoxin blocks the nicotinic stimulation of dopamine release from rat striatum. Neurosci. Letts. 98: 310–316.CrossRefGoogle Scholar
  38. Winn, P., Farrell, A., Maconick, A. & Robbins, T.W. 1983. Behavioural and pharmacological specificity of the feeding elicited by cholinergie stimulation of the substantia nigra in the rat. Behay. Neurosci. 97: 794–809.CrossRefGoogle Scholar
  39. Woolfe, N.J. & Butcher, L.L. 1986. Cholinergic systems in the rat brain. III. Projections from the pontomesencephalic tegmentum to the thalamus, tectum, basal ganglia, and basal forebrain. Brain. Res. Bull. 16: 603–637.CrossRefGoogle Scholar
  40. Yeomans, J.S., Kofman, 0. & McFarlane, V. 1984. Cholinergic involvement in lateral hypothalamic rewarding brain stimulation. Brain Res. 329: 19–26.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • M. G. Lacey
    • 1
    • 2
  • P. Calabresi
    • 1
    • 3
  • R. A. North
    • 1
  1. 1.Vollum InstituteOregon Health Sciences UniversityPortlandUSA
  2. 2.Department of PharmacologySmith Kline & French Research Ltd.Welwyn HertsUK
  3. 3.II Universita degli Studi di RomaRomeItaly

Personalised recommendations