Springer Nature is making Coronavirus research free. View research | View latest news | Sign up for updates

Cholinergic stimulation of substantia nigra: abolition of carbachol-induced eating by unilateral 6-hydroxydopamine lesion of nigrostriatal dopamine neurones

  • 31 Accesses

  • 14 Citations


Microinjection of cholinergic agonists into the substantia nigra is known to elicit increases in eating, drinking and sexual behaviour under appropriate circumstances. It has been suggested that these effects are dependent on stimulation of nigrostriatal dopamine-containing neurones in the substantia nigra pars compacta, but no direct evidence has confirmed this. The present experiment was therefore undertaken to determine whether unilateral lesions of nigrostriatal dopamine neurones made by 6-hydroxydopamine would attenuate or abolish eating in satiated rats elicited by intranigral microinjection of the muscarinic agonist carbachol. Two groups of rats were tested: a 6-hydroxydopamine- and a sham-lesion group. Before lesions were made intranigral microinjection of 0.5 μg/0.5 μl carbachol stimulated significantly more eating than control microinjections in both groups. After 6-hydroxydopamine lesions, microinjection of carbachol elicited no more eating than vehicle alone. Rats given sham lesions (ascorbate-saline vehicle only) showed increased feeding to intra-nigral carbachol before and after sham-lesioning. Post-mortem analysis by HPLC was used to determine the concentration of dopamine, DOPAC, HVA, serotonin and 5-HIAA in the lesioned and nonlesioned hemispheres of both 6-hydroxydopamine- and sham-lesioned rats. In caudate-putamen there were significant reductions in the concentration of DA (to 50.03% of the level in control sides), DOPAC (to 49.34%) and HVA (to 63.98%) in the 6-hydroxydopamine-lesioned but not sham-lesioned rats. The concentration of dopamine, DOPAC and HVA were not affected in the nucleus accumbens. The turnover of dopamine (assessed by calculating the ratio of dopamine to DOPAC) in the caudateputamen but not nucleus accumbens was also altered by the 6-hydroxydopamine lesions. The concentration and turnover of serotonin was not affected in either the caudate-putamen or nucleus accumbens in either group of rats. These data show that loss of dopamine from the caudate-putamen but not nucleus accumbens is sufficient to abolish completely the eating stimulated by intranigral carbachol.

This is a preview of subscription content, log in to check access.


  1. Beninato M, Spencer RF (1987) A cholinergic projection to the rat substantia nigra from the pedunculopontine tegmental nucleus. Brain Res 412: 169–174

  2. Beninato M, Spencer RF (1988) The cholinergic innervation of the rat substantia nigra: a light and electron microscopic immunohistochemical study. Exp Brain Res 72: 178–84

  3. Bolam JP, Francis CM, Henderson Z (1991) Cholinergic input to dopaminergic neurones in the substantia nigra: a double immunocytochemical study. Neuroscience 41: 483–494

  4. Butcher LL, Marchand R (1978) Dopamine neurones in pars compacta of the substantia nigra contain acetycholinesterase: histochemical correlations on the same brain section. Eur J Pharmacol 52: 415–417

  5. Carli M, Evenden JL, Robbins TW (1985) Depletion of unilateral striatal dopamine impairs initiation of contralateral actions and not sensory attention. Nature 313: 679–682

  6. Clarke PBS, Hommer DW, Pert A, Skirboll LR (1987) Innervation of substantia nigra neurons by cholinergic afferents from pedunculopontine nucleus in the rat: neuroanatomical and electrophysiological evidence. Neuroscience 23: 1011–9

  7. Clarke PBS, Pert A (1985) Autoradiographic evidence for nicotinic receptors on nigrostriatal and mesolimbic dopaminergic neurons. Brain Res 348: 355–358

  8. Clarke PBS, Schwartz RD, Paul SM, Pert CB, Pert A (1985) Nicotinic binding in rat brain: autoradiographic comparison of (3H)acetylcholine, (3H)nicotine and (125I)alpha-bungarotoxin. J Neurosci 5: 1307–1315

  9. Cross AJ, Waddington JL (1980) (3H) Quinuclidinyl benzylate and (3H) GABA receptor binding in rat substantia nigra after 6-hydroxydopamine lesions. Neurosci Lett 17: 271–275

  10. Dunnett SB, Lane DM, Winn P (1985) Ibotenic acid lesions of the lateral hypothalamus: comparison with 6-hydroxydopamine-induced sensorimotor deficits. Neuroscience 14: 509–518

  11. Gnadt JW, Pegram GV (1986) Cholinergic brainstem mechanisms and REM sleep in the rat. Brain Res 384: 29–41

  12. Gould E, Woolf NJ, Butcher LL (1989) Cholinergic projections to the substantia nigra from the pedunculopontine and laterodorsal tegmental nuclei. Neuroscience 28: 611–23

  13. Greenfleld SA, Cheramy A, Leviel V, Glowinski J (1980) In vivo release of acetylcholinesterase in cat substantia nigra and caudate nucleus. Nature 284: 355–357

  14. Heffner TG, Hartman JA, Seiden LS (1980) Feeding increases dopamine metabolism in the rat brain. Science 208: 1168–1170

  15. Hefti F, Melamed E, Sahakian BJ, Wurtman RJ (1980) Circling behavior in rats with partial, unilateral nigra-striatal lesions: effect of amphetamine, apomorphine, and DOPA. Pharmacol Biochem Behav 12: 185–188

  16. Jackson A, Crossman AR (1983) Nucleus tegmenti pedunculopontinus efferent connections with special reference to the basal ganglia, studied in the rat by anterograde and retrograde transport of horseradish peroxidase. Neuroscience 10: 725–766

  17. Jacobowitz DM, Goldberg AM (1977) Determination of acetylcholine in discrete regions of the rat brain. Brain Res 122: 575–577

  18. Jones DJ, Mogenson GJ (1979) Oral motor performance following central dopamine receptor blockade. Eur J Pharmacol 59: 11–21

  19. Kemp JA, Walker RJ, Woodruff GN (1977) The actions of cholinomimetics and catecholamines on rat substantia nigra neurones. Proc Br Pharmacol Soc 507–522

  20. Koob GF, Riley SJ, Smith C, Robbins TW (1978) Effects of 6-hydroxydopamine lesions of the nucleus accumbens septi and olfactory tubercle on feeding, locomotor activity and amphetamine anorexia in the rat. J Comp Physiol Psychol 92: 917–927

  21. Lacey MG, Calabresi P, North RA (1990) Muscarine depolarizes rat substantia nigra zona compacta and ventral tegmental neurons in vitro through M1-like receptors. J Pharmacol Exp Therap 253: 395–400

  22. Lee HJ, Rye DB, Hallanger AE, Levey AI, Wainer BH (1988) Cholinergic vs. non-cholinergic efferents from the mesopontine tegmentum to the extrapyramidal motor system nuclei. J Comp Neurol 275: 469–492

  23. Lehmann J, Fibiger HC (1978) Acetylcholinesterase in the rat substantia nigra and caudate-putamen of the rat: properties and localization in dopaminergic neurones. J Neurochem 30: 615–624

  24. Lichtensteiger W, Hefti F, Felix D, Huwyler T, Melamed E, Schlump M (1982) Stimulation of nigrostriatal neurones by nicotine. Neuropharmacology 21: 963–968

  25. Lin PYT, Blank CL (1983) Utilizing 3 μm reverse phase columns for LCEC determination of biogenic amines. Current Separations 5: 3–6

  26. Marshall JF, Richardson JS, Teitelbaum P (1974) Nigrostriatal bundle damage and the lateral hypothalamic syndrome. J Comp Physiol Psyschol 87: 808–830

  27. Marshall JF, Ungerstedt U (1977) Supersensitivity to apomorphine following destruction of the ascending dopamine neurons: quantification using the rotational model. Eur J Pharmacol 41: 361–367

  28. Mayer GS, Shoup RE (1983) Simultaneous multiple electrode liquid chromatographic electrochemical assay for catecholamines, indolemines and metabolites in brain tissue. J Chromatogr 255: 533–544

  29. Myers RD, Hoch DB (1978) 14C-dopamine microinjected into the brain-stem of the rat: dispersion kinetics, site content and functional dose. Brain Res Bull 3: 601–9

  30. Paxinos G, Watson C (1982) The rat brain in sterotaxic co-ordinates. Academic Press, New York

  31. Pope SG, Dean P, Redgrade P (1980) Dissociation of d-amphetamine-induced locomotor activity and stereotyped behaviour by lesions of the superior colliculus. Psychopharmacology 70: 297–302

  32. Redgrave P, Dean P, Donohoe TP, Pope SG (1980) Superior colliculus lesions selectively attenuate apomorphine-induced oral stereotypy: a possible role for the nigrotectal pathway. Brain Res 196: 541–546

  33. Rice ME, Gerhardt GA, Hierl PM, Nagy G, Adams RN (1985) Diffusion coefficients of neurotransmitters and their metabolites in brain extracellular fluid space. Neuroscience 15: 891–902

  34. Roth RH, Murrin LC, Walters JR (1976) Central dopaminergic neurons: effect of alterations of impulse flow on the accumulation of dihydroxyphenylacetic acid. Eur J Pharmacol 36: 163–171

  35. Ryan TA (1959) Multiple comparisons in psychological research. Phychol Bull 56: 26–47

  36. Scarnati E, Hajdu F, Pacitti C, Tombol T (1988) An EM and Golgi study on the connection between the nucleus tegmenti pedunculopontinus and the pars compacta of the substantia nigra in the rat. J Hirnforsch 29: 95–105

  37. Semba K, Reiner PB, Fibiger HC (1990) Single cholinergic mesopontine tegmental neurons project to both the pontine reticular formation and the thalamus in the rat. Neuroscience 38: 643–654

  38. Sharp T, Zetterstrom T, Ungerstedt U (1986) An in vivo study of dopamine release and metabolism in rat brain regions using intracerebral dialysis. J Neurochem 47: 113–122

  39. Steriade M, Llinas RR (1988) The functional states of the thalamus and the associated neuronal interplay. Physiol Rev 68: 649–742

  40. Taha EB, Redgrave P (1980) Neuroleptic suppression of feeding and oral stereotypy following microinjection of carbachol into substantia nigra. Neurosci Lett 20: 357–361

  41. Ungerstedt U (1971) Adipsia and aphagia after 6-hydroxydopamine induced degeneration of the nigrostriatal dopamine system. Acta Physiol Scand, Suppl 367: 95–122

  42. Westerink BHC (1979) Further studies on the sequence of dopamine metabolism in the rat. Eur J Pharmacol 56: 313–322

  43. Winn P (1990) Cholinergic stimulation of substantia nigra: effects on feeding, drinking and sexual behaviour in the male rat. Psychopharmacology (in press)

  44. Winn P, Farrell A, Maconick A, Robbins TW (1983) Behavioural and pharmacological specificity of the feeding elicited by cholinergic stimulation of the substantia nigra in the rat. Behav Neurosci 97: 794–809

  45. Winn P, Redgrave P (1979) Feeding following microinjection of cholinergic substances into substantia nigra. Life Sci 25: 333–338

  46. Winn P, Redgrave P (1981) Dose-dependent feeding in the rat following substantia nigra acetycholinesterase blockade. Eur J Pharmacol 76: 421–425

  47. Winn P, Williams SF, Herberg LJ (1982) Feeding stimulated by very low doses of d-amphetamine administered systemically or by microinjection into the striatum. Psychopharmacology 78: 336–341

Download references

Author information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Parker, G.C., Rugg, E.L. & Winn, P. Cholinergic stimulation of substantia nigra: abolition of carbachol-induced eating by unilateral 6-hydroxydopamine lesion of nigrostriatal dopamine neurones. Exp Brain Res 87, 597–603 (1991).

Download citation

Key words

  • Carbachol
  • Eating
  • Substantia nigra
  • 6-hydroxydopamine
  • Dopamine
  • HPLC