Neuropharmacology and Functional Anatomy of the Basal Ganglia: Experimental Models for Parkinson’s and Alzheimer’s Disease

  • Mario Herrera-Marschitz
  • Urban Ungerstedt
Part of the Advances in Behavioral Biology book series (ABBI, volume 38A)


The term Basal Ganglia refers to large subcortical nuclear masses considered to be derivatives of the forebrain. Significant progress in the understanding of the morphology and functional organization of the basal ganglia followed the demonstration and mapping of central monoamine neuron systems. Dopamine is an essential neurotransmitter in the basal ganglia. Indeed, the neostriatum is richly innervated by dopaminergic fibres originating in the pars compacta of the substantia nigra (Ungerstedt 1971, Lindvall & Björklund 1974), and this pathway constitutes a pivotal axis in the pathogenesis of Parkinson’s disease. A deficit in dopamine transmission is the most constant abnormality found in Parkinson’s disease (Hornykiewicz 1963). Classically the most conspicuous symptoms of Parkinson’s disease include akinesia and bradykinesia, rigidity and postural abnormalities, which can lead to skeletal deformities. Indeed, we have recently reported that discret lesions of the basal ganglia produce deformities of the spinal cord and scoliosis in rats (Herrera-Marschitz et al. 1990d). These skeletal deformities are in turn the causes of further impairments of motor behaviour. Thus, brain and peripheral systems interact when producing motor behaviour, in such a manner that causes and effects are reciprocally influenced.


Nerve Growth Factor Striatal Dopamine Nucleus Basalis Senile Dementia Striatal Dopamine Release 
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. Adolfsson R, GottfriesCG, Roos BE, Winblad B, 1979, Changes in the brain catecholamines in patients with dementia of Alzheimer type. Brit J Psychiat, 135: 216–223.Google Scholar
  2. Agnati LF, Fuxe K, Calza L, Benfenati F, Cavicchioli L, Toffano G, Goldstein M, 1983, Gangliosides increase the survival of lesioned nigral dopamine neurons and favour the recovery of dopaminergic synaptic function in striatum of rats by collateral spouting. Acta Physiol Scand, 119: 347–363.PubMedCrossRefGoogle Scholar
  3. Allen JM, Cross AJ, Crow TJ, Javoy-Agid F, Agid Y, Bloom SR, 1985, Dissociation of neuropeptide Y and somatostatin in Parksinson’s disease. Brain Research, 337: 197–200.PubMedCrossRefGoogle Scholar
  4. Boller F, Mizutani T, Roessmann U, Gambetti P, 1980, Parkinson disease, dementia, and alzheimer disease: Clinicopathological correlations. Ann Neurol, 7: 329–335.PubMedCrossRefGoogle Scholar
  5. Boyter JJ, Park DH, Joh Th, Pickel VM, 1984, Chemical and structural analysis of the relation between cortical inputs and tyrosine Hydroxylase-containing terminals in rat neostriatum, Brain Res, 302: 267–275.CrossRefGoogle Scholar
  6. Brown JIG, Marsden CD, 1986, Visuospatial function in Parkinson’s disease. Brain, 109: 987–1002.PubMedCrossRefGoogle Scholar
  7. Christensson-Nylander I, Herrera-Marschitz M, Staines W, Hökfelt T, Terenius L, Ungerstedt U, Cuello C, Oertel WH, Goldstein M, 1986, Striato-nigral dynorphin and substance P pathways in the rat. I: Biochemical and immunohistochemical studies. Exp Brain Res, 64: 169–192.PubMedCrossRefGoogle Scholar
  8. Coyle JT, Prince DL, DeLong MR, 1983, Alzheimer’s disease: A disorder of cortical cholinergic innervation. Science, 219: 1184–1190.PubMedCrossRefGoogle Scholar
  9. Cross AJ, Crow TJ, Perry EK, Perry RH, Blessed G, Tomlinson BE, 1981, Reduced dopamine-betahydroxylase activity in Alzheimer’s disease. Br Medical J. 282: 93–94.CrossRefGoogle Scholar
  10. Cuello AC, Stephens PH, Tagari PC, Sofroniew MV, Pearson RCA, 1986, Retrograde changes in the nucleus basalis of the rat, caused by cortical damage, are prevented by exogenous ganglioside GM. Brain Res, 376: 373–377.CrossRefGoogle Scholar
  11. Davies P, 1979, Neurotransmitter related enzymes in senile dementia of the Alzheimer type. Brain Res, 171: 319–327.PubMedCrossRefGoogle Scholar
  12. Davies P, Katzman R, Terry RD, 1980, Reduced somatostatin-like immunoreactivity in cerebral cortex from cases of Alzheimer disease and Alzheimer senile dementia. Nature, vol 288: 279–280.PubMedCrossRefGoogle Scholar
  13. Epelbaum-J, Ruberg M, Moyse E, Joavoy-Agid F, Dubois B, Agid Y, 1983, Somatostatin and dementia in Parkinson’s disease. Brain Res, 278: 376–379.CrossRefGoogle Scholar
  14. Ferre S, Guix T, Salles J, Badia A, Parra P, Jane F, Herrera-Marschitz M, Ungerstedt U, Casas M, 1990. Paraxanthine, the main metabolite of caffeine in man, is a Dl dopaminergic agonist in rat. Eur J Pharmacol, in press.Google Scholar
  15. Giorguieff MF, Kemel ML, Glowinski J, 1977, Presynaptic effect of L-glutamic acid on the release of dopamine in rat striatal slices. Neuroscience Lett, 6: 73–77.CrossRefGoogle Scholar
  16. Graybiel AM, Ragsdale CW, 1983, Biochemical anatomy of the striatum. In:PC Emson (ed) Chemical Neuroanatomy. Raven Press, New York, pp:427–504.Google Scholar
  17. Hakim AM, Mathieson G, 1979, Dementia in Parkinson disease: A neuropathologic study, Neurology, 29: 1209–1214.PubMedCrossRefGoogle Scholar
  18. Herrera-Marschitz M, 1990, Modulation of striatal dopamine and acetylcholine release by different glutamate receptors: studies with in vivo microdialysis. In: G. Bernardi, M.H. Carpenter, G. Di Chiara (eds) Basal ganglia I II, Plenum Publ. Corp., New York.Google Scholar
  19. Herrera-Marschitz M, Christensson-Nylander I, Sharp T, Staines W, Reid M, Hökfelt T, Terenius L, Ungerstedt U, 1986, Striato-nigral dynorphin and substance P pathways in the rat. II: Functional analysis. Exp Brain Res, 64: 193–207.PubMedCrossRefGoogle Scholar
  20. Herrera-Marschitz M, Nylander I, Reid M, Sharp T, Hökfelt T, Terenius L, Ungerstedt U, 1987, Different functional roles for substance P and dynorphin in the striato-nigral pathway of rat. In: J Henry, R Couture, C Cuello, G Pelletier, R Quirion, and D Regoli (eds) Substance P and Neurokinins, Springer-Verlag, New York, pp: 353–355.Google Scholar
  21. Herrera-Marschitz M, Casas M, Ungerstedt U, 1988, Caffeine produces contralateral rotation in rats with unilateral dopamine denervation: comparisons with apomorphine-induced responses. Psychopharmacology, 94: 38–45.PubMedCrossRefGoogle Scholar
  22. Herrera-Marschitz M, Goiny M, Utsumi H, Ungerstedt U, 1989, Mesencephalic dopamine innervation of the frontoparietal (sensorimotor) cortex of the rat: a microdialysis study. Neuroscience Letters, 97: 266–270.PubMedCrossRefGoogle Scholar
  23. Herrera-Marschitz M, Goiny M, Utsumi H, Ferre S, Guix T, Ungerstedt U, 1990a, Regulation of cortical and striatal dopamine and acetylcholine by glutamate mechanisms assyed in vivo with microdialysis: in situ stimulation with kainate-, quisqualate- and NMDA-receptor agonists. Amino Acids: Chemistry, Biology and Medicine, 1: 599–604.Google Scholar
  24. Herrera-Marschitz M, Goiny M, Utsumi H, Ferre S, Häkansson L, Nordberg A, Ungerstedt U, 1990b, Effect of unilateral nucleus basalis lesion on cortical and striatal acetylcholine dopamine release monitored with microdialysis. Neuroscience Letters, in press.Google Scholar
  25. Herrera-Marschitz M, Terenius L, Reid M, Ungerstedt U, 1990c, The substance P (1–7) fragment is a potent modulator of substance P actions in the brain. Brain Res, in press.Google Scholar
  26. Herrera-Marschitz M, Utsumi H, Ungerstedt U, 1990d, Scoliosis in rats with experimentally-induced hemiparkinsonism: dependence upon striatal dopamine denervation. Journal of Neurology, Neurosurgery and Psychiatry, 53: 39–43.CrossRefGoogle Scholar
  27. Herrling PL, 1985, Pharmacology of the corticocaudate excitatory postsynaptic potential in the cat: Evidence for its mediation by quisqualate-or kainate-receptors. Neuroscience, 14: 417–426.PubMedCrossRefGoogle Scholar
  28. Hornykiewicz O, 1963, Die topische Lokalisation und das Verhalten von Noradrenalin und Dopamin (3-hydroxytyramin) in der Substantia Nigra des Normalen und Parkinson-kranken Menschen, Wien Klin Wischr, 75: 309–312.Google Scholar
  29. Hökfelt T, Millhorn D, Seroogy K, Tsuruo Y, Ceccatelli S, Lindh B, Meister B, Melander T, Schalling M, Bartfai T, Terenius L, 1987, Coexistence of peptides with classical neurotransmitters, Experientia, 43: 768–780.PubMedCrossRefGoogle Scholar
  30. Lindefors N, Brene S, Herrera-Marschitz M, Persson H, 1989, Region specific regulation of glutamic acid decarboxylase mRNA expression by dopamine neurons in rat brain, Exp Brain Res, 77: 611–620.PubMedCrossRefGoogle Scholar
  31. Lindefors N, Brene S. Herrera-Marschitz M, Persson H, 1990, Neuropeptide gene expression in brain is differently regulated by midbrain dopamine neurons. Experimental Brain Research, in press.Google Scholar
  32. Lindvall O, Björklund A, 1974, The organization of the ascending catecholamine neuron systems in the rat brain as revealed by the glyoxylic acid fluorescence method. Acta Physiol Scand, Suppl 412: 1–48.Google Scholar
  33. Maysinger D, Herrera-Marschitz M, Carlsson A, Garofalo L, Cuello AC, Ungerstedt U, 1988, Striatal and cortical acetylocholine release in vivo in rats with unilateral decortication: effects of treatment with monosialoganglioside GM1. Brain Res, 461: 355–360.CrossRefGoogle Scholar
  34. Maysinger D, Herrera-Marschitz M, Karlsson A, Garofalo L, Ungerstedt U, Cuello AC, 1989, Effect of monosialoganglioside GM1 on acetylcholine release in vivo after devascularizing cortical lesions. Neuropharmacology, 29: 151–159.CrossRefGoogle Scholar
  35. Mesulam, MM, Mufson EJ, Wainer BH, Levey AL, 1983, Central cholinergic pathways in the rat: An overview based on an alternative nomenclature (Chl-Ch6). Neuroscience, 10: 1185–1201.PubMedCrossRefGoogle Scholar
  36. Mesulam MM, Mufson EJ, 1984 Neural inputs into the nucleus basalis of the substantia innominata (Ch-4) in the rhesus monkey. Brain, 107: 253–274.PubMedCrossRefGoogle Scholar
  37. Pearson RCA, Gatter KC, Powell TPS, 1983, Retrograde cell degeneration in the basal nucleus in monkey and man. Brain Res, 261: 321–326.PubMedCrossRefGoogle Scholar
  38. Reid M, Herrera-Marschitz M, Hökfelt T, Terenius L, Ungerstedt U, 1988, Differential modulation of striatal dopamine release by intranigral injection of gamma-aminobutyric acid (GABA), dynorphin A, substance P. Eur J Pharmacol, 147: 411–420.PubMedCrossRefGoogle Scholar
  39. Reid SM, Herrera-Marschitz M, Terenius L and Ungerstedt U, 1989, Intranigral substance P modulation of striatal dopamine: interaction with N-terminal and C-terminal substance P fragments, Brain Res, in press.Google Scholar
  40. Reid MS, Herrera-Marschitz M, Hökfelt T, Ohlin M, Valentino KL, Ungerstedt U, 1990a, Effects of intranigral substance P and neurokinin A on striatal dopamine release: I. Interactions with substance P antagonists. Neuroscience, in press.Google Scholar
  41. Reid MS, O’Connor WT, Herrera-Marschitz M, Ungerstedt U, 1990b, The effects of intranigal GABA and dynorphin A injections on striatal dopamine and GABA release: evidence that dopamine provides inhibitory regulation of striatal GABA neurons via D2 receptors. Brain Res, in press.Google Scholar
  42. Sofroniew MV, Pearson RCA, Eckenstein F, Cuello AC, Powell TPS, 1983, Retrograde changes in cholinergic neurons in the basal forebrain of the rat following cortical damage. Brain Research, 289: 370–374.PubMedCrossRefGoogle Scholar
  43. Strömberg I, Herrera-Marschitz M, Ungerstedt U, Ebendal T, Olson L, 1985, Chronic implants of chromaffin tissue into the dopamine-denervated striatum. Effects of NGF on graft survival, fiber growth and rotational behaviour. Exp Brain Res, 60: 335–349.PubMedCrossRefGoogle Scholar
  44. Taylor AE, Saint-Cyr JA, Lang AE, 1986, Frontal lobe dysfunction in Parkinson’s disease. Brain, 109: 845–883.PubMedCrossRefGoogle Scholar
  45. Taylor AE, Saint-Cyr JA, Lang AE, 1987, Parkinson’s disease cognitive changes in relation to treatment response. Brain, 110: 35–51.PubMedCrossRefGoogle Scholar
  46. Terry RD, Davies P, 1980, Dementia of the Alzheimer type. Ann Rev Neurosci, 3: 77–95.PubMedCrossRefGoogle Scholar
  47. Ungerstedt U, 1971, Stereotaxic mapping of the monamine pathway in the rat brain. Acta Physiol Scand, suppl 367: 1–48.Google Scholar
  48. Ungerstedt U, Arbuthnott GW, 1970, Quantitative recording of rotational behaviour in rats after 6-hydroxy-dopamine lesions of the nigrostriatal dopamine system. Brain Res, 24: 485–493.PubMedCrossRefGoogle Scholar
  49. Walaas I, 1981, Biochemical evidence for overlapping neocortical and allocortical glutamate projections to the nucleus accumbens and rostral caudtoputamen in rat brain. Neuroscience, 6: 399–405.PubMedCrossRefGoogle Scholar
  50. Whitehouse PJ, 1987, Neurotransmitter receptor alterations in Alzheimer disease: A review. Alzheimer disease and associated disorders, 1 (1): 9–18.PubMedCrossRefGoogle Scholar
  51. Whitehouse PJ, Price DL, Clark AW, Coyle JT, DeLong MR, 1980, Alzheimer disease: Evidence for selective loss of cholinergic neurons in the nucleus basalis. Ann Neurol, 10: 122–126.CrossRefGoogle Scholar
  52. Whitehouse PJ, Prince DL, Struble RG, Clark AW, Coyle JT, DeLong MR, 1982, Alzheimer’s disease and senile dementia: Loss of neurons in the basal forebrain. Science, 215: 1237–1239.PubMedCrossRefGoogle Scholar
  53. Woolf NJ, Eckenstein F, Butcher LL, 1983, Cholinergic projections from the basal forebrain to the frontal cortex: A combined fluorescent tracer and immunohistochemical analysis in the rat. Neuroscience Letts, 40: 93–98.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • Mario Herrera-Marschitz
    • 1
  • Urban Ungerstedt
    • 1
  1. 1.Department of PharmacologyKarolinska institutetStockholmSweden

Personalised recommendations