Hostname: page-component-84b7d79bbc-fnpn6 Total loading time: 0 Render date: 2024-07-26T12:20:57.069Z Has data issue: false hasContentIssue false
  • English
  • Français

Synergistic Interactions of D1- and D2-Selective Dopamine Agonists in Animal Models for Parkinson’s Disease: Sites of Action and Implications for the Pathogenesis of Dyskinesias

Published online by Cambridge University Press:  18 September 2015

H.A. Robertson
H.A. Robertson*
Affiliation:
Departments of Pharmacology and Medicine (Neurology), Faculty of Medicine, Dalhousie University, Halifax
*
Departments of Pharmacology and Medicine, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4H7
Rights & Permissions [Opens in a new window]

Abstract:

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

The addition of a D2 agonist such as bromocriptine to L-Dopa therapy can often improve the response of patients with Parkinson’s disease dramatically. Simultaneous activation of D1 and D2 dopamine receptors can produce a synergistic effect on locomotion in rats and primates. However, despite the importance of this addition of a D2 agonist to the D1/D2 agonist L-Dopa, little is known of the sites of action of these agents. Recent work suggests that, in addition to D1 and D2 dopamine receptor sites in the striatum (caudate-putamen), L-Dopa and D1 agonists have important effects at D1 dopamine receptors in the substantia nigra. Animal experiments suggest that D1 and D2 dopamine receptor agonists probably also affect different outflow pathways from the striatum. An understanding of these pathways and how dopamine agonists affect them gives insight into some of the clinical problems experienced in treating Parkinson’s disease (the “on-off phenomenon, for example). D1/D2 dopamine receptors also differentially affect gene expression and regulation in the striatum. An understanding of the anatomical and biochemical location of the actions of dopamine receptor agonists will be important in maximizing the beneficial effects and minimizing the side-effects of both presently-used drugs and new treatments.

Type
Research Article
Information
Canadian Journal of Neurological Sciences , Volume 19 , Issue S1: 3rd Canadian Conference on Neurodegenerative Diseases , February 1992 , pp. 147 - 152
Copyright
Copyright © Canadian Neurological Sciences Federation 1992

References

1.Kebabian, JW, Calne, DB.Multiple receptors for dopamine. Nature 1979; 277: 93–96.CrossRefGoogle ScholarPubMed
2.Sokoloff, P, Giros, B, Martres M-P, et al. Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics. Nature 1990; 347: 146–151.CrossRefGoogle Scholar
3.Ungerstedt, U.Postsynaptic supersensitivity after 6-hydroxy-dopamine induced degeneration of the nigrostriatal dopamine system. Acta Physiol Scand 1971; 367 (Suppl): 69–101.CrossRefGoogle Scholar
4.Cheramy, A, Leviel, V, Glowinski, J.Dendritic release of dopamine in the substantia nigra. Nature 1981; 289: 537–542.CrossRefGoogle ScholarPubMed
5.Quik, M, Emson, PC, Joyce, E.Dissociation between the presynaptic dopamine sensitive adenylate cyclase and (3H) spiperone binding sites in substantia nigra. Brain Res 1979; 167–335–365.Google ScholarPubMed
6.Murrin, LC, Gale, K, Kuhar, MJ.Autoradiographic localization of neuroleptic and dopamine receptors in the caudate-putamen and substantia nigra: effects of lesions. Eur J Pharmacol 1979; 60: 229–235.CrossRefGoogle ScholarPubMed
7.Boyson, SJ, McGonigle, P, Molinoff, PB.Quantitative autoradiographic localization of the D1 and D2 subtypes of dopamine receptors in rat brain. J Neurosci 1986; 6: 3177–3188.CrossRefGoogle ScholarPubMed
8.Savasta, M, Dubois, A, Benavides, J, et al. Different neuronal location of (3H)SCH 23390 binding sites in pars reticulata and pars compacta of the substantia nigra in the rat. Neurosci Lett 1986; 72: 265–271.CrossRefGoogle Scholar
9.Missale, C, Nisoli, E, Liberini, P, et al. Repeated reserpine administration up-regulates the transduction mechanism of D, receptors without changing the density of (3H)SCH 23390 binding. Brain Res 1989; 483: 117–122.CrossRefGoogle Scholar
10.Robertson, GS, Robertson, HA.Synergistic effects of D2 and D2 dopamine agonists on turning behaviour in rats. Brain Res 1986; 384: 384–387.CrossRefGoogle ScholarPubMed
11.Jackson, DM, Hashizume, M.Bromocriptine induces marked locomotor stimulation in dopamine-depleted mice when D-1 dopamine receptors are stimulated with SKF 38393. Psychopharmacology 1986; 90: 147–153.CrossRefGoogle Scholar
12.Rouillard, C, Bedard, PJ.Specific D1 and D2 dopamine agonists have synergistic effects in the 6-hydroxydopamine circling model in the rat. Neuropharmacology 1988; 27: 1257–1264.CrossRefGoogle ScholarPubMed
13.Sonsalla, PK, Manzino, L, Heikkila, RE.Interactions of D1 and D2 dopamine receptors on the ipsilateral vs contralateral side in rats with unilateral lesions of the dopaminergic nigrostriatal pathway. J Pharmacol Exp Ther 1988; 247: 180–185.Google ScholarPubMed
14.Robertson, HA, Robertson, GS.Combined L-Dopa and bromocriptine therapy for Parkinson’s disease: a proposed mechanism of action. Clin Neuopharmacol 1987; 10: 384–387.CrossRefGoogle ScholarPubMed
15.Robertson, GS, Robertson, HA.D1 and D2 dopamine agonist synergism: separate sites of action. Trends Pharmacol Sci 1987; 8: 295–299.CrossRefGoogle Scholar
16.Clark, D, White, FJ.Review: D1 dopamine receptor–the search for a function: a critical evaluation of the D1/D2 dopamine receptor classification and its functional implications. Synapse 1987; I: 347–388.CrossRefGoogle Scholar
17.Robertson, GS, Robertson, HA.Evidence that the substantia nigra is a site of action for L-Dopa. Neurosci Lett 1988; 89: 204–209.CrossRefGoogle ScholarPubMed
18.Robertson, GS, Robertson, HA.L-Dopa induced rotational behaviour is dependent on both striatal and nigral mechanisms. J Neurosci 1989; 9: 3326–3331.CrossRefGoogle ScholarPubMed
19.Weick, BG, Walters, JR.Effects of D1 and D2 dopamine receptor stimulation on the activity of substantia nigra pars reticulata neurons in 6-hydroxydopamine lesioned rats: D1/D2 coactivation induces potentiated responses. Brain Res 1987; 405: 234–246.CrossRefGoogle ScholarPubMed
20.Aceves, J, Floran, B, Martinez-Fong, D, et al. L-Dopa stimulates the release of (3H)gamma-aminobutyric acid in the basal ganglia of 6-hydroxydopamine lesioned rats. Neurosci Lett 1991; 121: 223–226.CrossRefGoogle Scholar
21.Trugman, JM, Wooten, GF.Selective D-1 and D-2 dopamine agonists differentially alter basal ganglia glucose utilization in rats with unilateral 6-hydroxydopamine substantia nigra lesions. J Neurosci 1987; 7: 2927–2935.CrossRefGoogle Scholar
22.Hu, X-T, Wachtel, SR, Galloway, MP, et al. Lesions of the nigrostriatal dopamine projection increase the inhibitory effects of D1 and D2 dopamine agonists on caudate-putamen neurons and relieve D2 receptors from the necessity of D1 receptor stimulation. J Neurosci 1990; 10: 2318–2329.CrossRefGoogle ScholarPubMed
23.LaHoste, GJ, Marshall, JF.Nigral D1 and striatal D2 receptors mediate the behavioral effects of dopamine agonists. Behav Brain Res 1990; 38: 233–242.CrossRefGoogle ScholarPubMed
24.Spencer, SE and Wooten, GF.Pharmacologic effects of L-Dopa are not closely linked temporally to striatal dopamine concentration. Neurology 1984; 4: 1609–1611.CrossRefGoogle Scholar
25.Zetterstrom, T, Herrera-Marschitz, M, Ungerstedt, U.Simultaneous measurement of dopamine release and rotational behaviour in 6-hydroxydopamine denervated rats using intracerebral dialysis. Brain Res 1986; 376: 1–7.CrossRefGoogle ScholarPubMed
26.Herrera-Marschitz, M, Ungerstedt, U.Evidence that striatal efferents relate to different dopamine receptors. Brain Res 1984; 323: 269–278.CrossRefGoogle ScholarPubMed
27.Herrera-Marschitz, M, Ungerstedt, U.Effect of the dopamine D-1 antagonist SCH 23390 on rotational behaviour induced by apomorphine and pergolide in 6-hydroxydopamine denervated rats. Eur J Pharmacol 1985; 109: 49–54.CrossRefGoogle Scholar
28.Graybiel, AM.Neurotransmitters and neuromodulators in the basal ganglia. Trends Neurosci 1990; 13: 244–254.CrossRefGoogle ScholarPubMed
29.Gerfen, CR, Engber, TM, Mahan, LC, et al. D1 and D2 dopamine receptor-regulated gene expression of striatonigral and striato-pallidal neurons. Science 1990; 250: 1429–1432.CrossRefGoogle Scholar
30.Bedard, PJ, Di Paola, T, Falardeau, P, et al. Chronic treatment with levodopa but not bromocriptine induces dyskinesia in MPTP-treated monkeys. Correlation with 3H-spiperone binding. Brain Res 1986; 379: 294–299.CrossRefGoogle ScholarPubMed
31.Moudranian, MM, Juncos, JL, Fabbrini, G, et al. Motor fluctuations in Parkinson’s disease: pathogenetic and therapeutic studies. Ann Neurol 1988; 22: 475–479.Google Scholar
32.Moudranian, MM, Juncos, JL, Fabbrini, G, et al. Motor fluctuations in Parkinson’s disease: central pathophysiological mechanisms, part II. Ann Neurol 1988; 24: 372–378.Google Scholar
33.Weick, BG, Engber, TM, Susel, Z, et al. Responses of substantia nigra pars reticulata neurons to GABA and SKF 38393 in 6-hydroxydopamine-lesioned rats are differentially affected by continuous and intermittent levodopa administration. Brain Res 1990; 523: 16–22.CrossRefGoogle ScholarPubMed
34.Lees, AJ, Stern, GM.Sustained bromocriptine therapy in previously untreated patients with Parkinson’s disease. J Neurol Neurosurg Psychiatry 1981; 44: 1020–1023.CrossRefGoogle ScholarPubMed
35.Robertson, GS, Herrera, DG, Dragunow, M, et al. L-Dopa activates c-fos expression in the striatum of 6-hydroxydopamine-lesioned rats. Eur J Pharmacol 1989; 159: 99–100.CrossRefGoogle Scholar
36.Robertson, HA, Peterson, MR, Murphy, K, et al. D1 dopamine receptor agonists selectively activate striatal c-fos independent of rotational behaviour. Brain Res 1989; 503: 346–349.CrossRefGoogle ScholarPubMed
37.Robertson, HA, Dragunow, M.From synapse to genome: the role of immediate-early genes in permanent alterations in the central nervous system. In: Osborne, NN, ed. Current Aspects of the Neuro-Sciences, 1990; 2: 143–157.Google Scholar
38.Robertson, HA, Paul, ML, Moratalla, R, et al. Expression of the immediate early gene c-fos in basal ganglia: induction by dopaminergic drugs. Can J Neurol Sci 1991; 18: 380–383.CrossRefGoogle ScholarPubMed
39.Graybiel, AM, Moratalla, R, Robertson, HA.Amphetamine and cocaine induced drug-specific activation of the c-fos gene in striosome-matrix and limbic subdivisions of the striatum. Proc Natl Acad Sci USA 1990; 87: 6912–6916.CrossRefGoogle ScholarPubMed
40.Young, ST, Porrino, LJ, Iadarola, MJ.Cocaine induces striatal c-fos- immunoreactive proteins via dopaminergic D1 receptors. Proc Natl Acad Sci USA 1991; 88: 1291–1295.CrossRefGoogle ScholarPubMed
41.Dragunow, M, Robertson, GS, Faull, RLM, et al. Haloperiodol induces an accumulation of c-fos-like protein in rat striatal neurons: NMDA receptor mediation. Neuroscience 1990; 37: 287–294.CrossRefGoogle Scholar
42.Robertson, GS, Vincent, SR, Fibiger, HC.Striatonigral projection neurons contain D1 dopamine receptor-activated c-fos. Brain Res 1990; 523: 288–290.CrossRefGoogle ScholarPubMed