Summary
Striatal mRNA expression for preproenkephalin (PPE) and preprotachykinin (PPT) was studied in unilateral 6-OHDA lesioned rats treated subchronically with a range of selective and non-selective D-1 or D-2 dopamine (DA) agonists. Apomorphine (5mg/kg sc), pergolide (0.5mg/kg sc), SKF 38393 (5mg/kg sc), SKF 80723 (1.5mg/kg sc), and quinpirole (5mg/ kg sc), or 0.9% saline (150μl sc) were all given twice daily (except pergolide: once daily) for 7 days. The abundance of PPE mRNA was not altered by any of these DA agonists in the intact striatum contralateral to the 6-OHDA lesion. Only apomorphine and quinpirole increased the abundance of PPT mRNA in the intact striatum. In saline treated 6-OHDA lesioned animals PPE mRNA was elevated (+160%, p < 0.005) and PPT mRNA decreased (−36%, p < 0.005) in the denervated striatum. The up-regulation of striatal PPE mRNA in the lesioned striatum was reversed only by pergolide. The downregulation of striatal PPT mRNA in the lesioned striatum was reversed only by apomorphine. The differential sensitivity of the striatal PPE message to the long-acting DA agonist pergolide, and of the striatal PPT message to the mixed D-1/D-2 DA agonist apomorphine suggests that the striatopallidal enkephalinergic pathways are mainly regulated by prolonged DA receptor stimulation, whereas the striatonigral substance P pathways are mainly regulated by mixed D-1/D-2 DA receptor stimulation.
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References
Angulo A, Davis L, Buckart B, Christoph G (1986) Reduction of striatal dopaminergic transmission elevates striatal proenkephalin mRNA. Eur J Pharmacol 130: 341–343
Angulo JA (1992) Involvement of dopamine D1 and D2 receptors in the regulation of proenkephalin mRNA abundance in the striatum and accumbens of the rat brain. J Neurochem 58: 1104–1109
Augood SJ, Emson P, Mitchell IJ, Boyce S, Clarke CE, Crossman AR (1989) Cellular localisation of enkephalin gene expression in MPTP-treated cynomolgus monkeys. Mol Brain Res 6: 85–92
Augood SJ, Faull RLM, Emson PC (1992) Contrasting effects of raclopride and SCH 23390 on the cellular content of preproenkephalin A mRNA in rat striatum: a quantitative non-radioactive in situ hybridization study. Eur J Neurosci 4: 102–112
Beckstead RM (1988) Association of dopamine D1 and D2 receptors with specific cellular elements in the basal ganglia of the cat: the uneven topography of dopamine receptors in the striatum is determined by intrinsic striatal cells, not nigrostriatal axons. Neuroscience 27: 851–863
Blunt SB, Jenner P, Marsden CD (1991) The effect of L-DOPA and carbidopa treatment on the survival of rat fetal dopamine grafts assessed by tyrosine hydroxylase immunohistochemistry and 3H-mazindol autoradiography. Neuroscience 43: 95–110
Caboche J, Vernier P, Julien J-F, Rogard M, Mallet J, Besson M-J (1991) Parallel decrease of glutamic acid decarboxylase snd preproenkephalin mRNA in the rat striatum following chronic treatment with a dopaminergic D1 antagonist and D2 agonist. J Neurochem 56: 428–435
Chen JF, Aloyo VJ, Weiss B (1993) Continous treatment with the D2 dopamine receptor agonist quinpirole decreases D2 dopamine receptors, D2 dopamine receptor messenger RNA and proenkephalin messenger RNA, and increases MU opioid receptors in mouse striatum. Neuroscience 54: 669–680
Deniau JM, Lackner D, Feger J (1978) Effect of substantia nigra stimulation on identified neurons in the VL-VA thalamic complex: comparison between intact and chronically decorticated cats. Brain Res 145: 27–35
Dermon CR, Pizzarro P, Georgopoulos P, Savaki HE (1990) Bilateral alterations in local cerebral glucose utilization following intranigral application of the GABAergic agonist muscimol. J Neurosci 10: 2861–2878
Dermon CR, Tzagournissakis, Savaki HE (1992) Bilateral cerebral metabolic effects of pharmacologic manipulation of the substantia nigra in the rat: unilateral intranigral application of the putative excitatory neurotransmitter substance P. Neuroscience 50: 795–809
Factor SA, Sanchez Ramos JR, Weiner WJ (1988) Parkinson's disease: an open label trial of pergolide in patients failing bromocriptine therapy. J Neurol Neurosurg Psychiatry 51: 529–533
Faull RLM, Mehler WR (1978) The cells of origin of nigrotectal, nigrothalamic and nigrostriatal projections in the rat. Neuroscience 3: 989–1002
Fuller RW, Clemens JA (1991) Pergolide: a dopamine agonist at both D1 and D2 receptors. Life Sci 49: 925–930
Gerfen CR, Staines WA, Arbuthnott GW, Fibiger HC (1982) Crossed connections of the substantia nigra in the rat. J Comp Neurol 207: 283–303
Gerfen CR, Engber TM, Mahan LC, Susel Z, Chase TN, Monsma FJ (1990) D1 and D2 dopamine receptor-regulated gene expression of striatonigral and striatopallidal neurons. Science 250: 1429–1432
Gerfen CR, McGinty JF, Young WS (1991) Dopamine differentially regulates dynorphin, SP, and enkephalin expression in striatal neurons: in situ hybridization histochemical analysis. J Neurosci 11: 1016–1031
Girault JA, Savaki HE, Desban M, Glowinski J, Besson MJ (1985) Bilateral cerebral metabolic alterations following lesion of the ventromedial thalamic nucleus: mapping by the 14C-deoxyglucose method in conscious rats. J Comp Neurol 231: 137–149
Gnanalingham KK, Erol DD, Hunter AJ, Smith LA, Jenner P, Marsden CD (1995) The differential antiparkinsonian effects of benzazepine D-1 dopamine agonists with varying efficacies in the MPTP-treated common marmoset. Psychopharmacology 117: 275–286
Goetz CG, Tanner CM, Glantz RH, Klawans HL (1985) Chronic agonist therapy for Parkinson's disease: a 5 years study of bromocriptine and pergolide. Neurology 35: 749–751
Goldstein M, Lieberman A, Lew JY, Asano T, Rosenfeld MR, Makman HM (1980) Interaction of pergolide wiyh central dopaminergic receptors. Proc Natl Acad Sci USA 77: 3725–3728
Hanson GR, Alphs L, Pradhan S, Lovenberg W (1981) Response of striatonigral SP system to a dopamine receptor agonist and antagonist. Neuropharmacology 20: 541–548
Haverstick D, Rubenstein A, Bannon M (1989) Striatal tachykinin gene expression regulated by interaction of D1 and D2 dopamine receptors. J Pharmcol Exp Ther 248: 858–862
Herrera-Marschitz M, Ungersted U (1984) Evidence that apomorphine and pergolide induce rotation in rats by different actions on D1 and D2 receptor sites. Eur J Pharmacol 98: 165–176
Hurd YL, Herkenham M (1992) Influence of a single injection of cocaine, amphetamine or GBR 12909 on mRNA expression of striatal neuropeptides. Mol Brain Res 16: 97–104
Ingham CA, Hood SH, Arbuthnott GW (1991) A light and electron microscopy study of enkephalin-immunoreactive structures in the rat neostriatum after removal of the nigrostiatal dopaminergic pathway. Neuroscience 42: 715–730
Jolkkonen J, Granata R, Jenner P, Marsden CD (1995) Acute and subchronic effects of dopamine agonists on neuropeptide gene expression in the rat striatum. Neuropeptides 29: 109–114
Krause JE, Chirgin JM, Carter MS, Xu ZS, Hershey AD (1987) Three rat preprotachykinin mRNAs encode the neuropeptides SP and neurokin A. Proc Natl Acad Sci USA 84: 881–885
Langtry HD, Clissold SP (1990) Pergolide: a review of its pharmacological properties and terapeutic potential in Parkinson's disease. Drugs 39: 491–506
Li SJ, Svivam SP, McGinty JF, Huang YS, Hong JS (1987) Dopaminergic regulation of tachykinin metabolism in the striatonigral pathway. J Pharmacol Exp Ther 243: 792–298
Li SJ, Jiang HA, Stachowiak MS, Hudson PM, Owyang V, Nanry K, Tilson HA, Hong JS (1990) Influence of nigrostriatal dopaminergic tone on the biosynthesis of dynorphin and enkephalin in rat striatum. Mol Brain Res 8: 219–225
Manier M, Abrous DN, Feuerstein C, Le Moal M, Herman JP (1991) Increase of striatal methionin enkephalin content following lesion of the nigrostriatal dopaminergic pathway in adult rats and reversal following the implantation of embryonic dopaminergic neurons: a quantitative immunohistochemical analysis. Neuroscience 42: 247–439
Moine Le C, Normand E, Guitteny AF, Fouque B, Teoule R, Bloch B (1990) Dopamine receptor gene expression by enkephalin neurons in rat forebrain. Proc Natl Acad Sci 87: 230–234
Morris BJ, Herz A, Holt V (1989) Localization of striatal opioid gene expression, and its modulation by the mesostriatal dopamine pathway: an in situ hybridisation study. J Mol Neurosci 1: 9–18
Normand E, Popovici T, Onteniente B, Fellman D, Piatier-Tonneau D, Auffray C, Bloch B (1988) Dopaminergic neurons of the substantia nigra modulate preproenkephalin A gene expression in rat striatal neurons. Brain Res 439: 39–46
Pollack AE, Wooten GF (1992) D2 dopaminergic regulation of striatal preproenkephalin mRNA levels is mediated at least in part through cholinergic interneurons. Mol Brain Res 13: 35–41
Romo R, Cheramy A, Godeheu G, Glowinsky J (1992) In vivo presynaptic control of dopamine release in the cat caudate nucleus. III. Further evidence for the implication of corticostriatal glutamatergic neurons. Ann Neurol 32: 151–61
Savaki HE, Desban M, Glowinski J, Besson MJ (1983) Local cerebral glucose consumption in the rat. II. Effects of unilateral substantia nigra stimulation in conscious and in halothane-anesthetized animals. J Comp Neurol 213: 46–65
Savaki HE, Girault JA, Desban M, Glowinski J, Besson MJ (1984) Local cerebral metabolic effects induced by nigral stimulation following ventromedial thalamic lesions. I. Basal ganglia and related motor structures. Brain Res Bull 12: 609–616
Savaki HE, Raos VC, Dermon CR (1992) Bilateral cerebreal metabolic effects of pharamcological manipulation of the substantia nigra in the rat: unilateral intranigral application of the inhibitory GABA A receptor agonist muscimol. Neuroscience 50: 166–173
Schwartz JC, Giros B, Martres MP, Sokoloff P (1992) The dopamine receptor family: molecular biology and pharmacology. Sem Neurosci 4: 99–108
Sirinathsinghji DJS, Dunnet SB (1991) Increased proenkephalin mRNA levels in the rat neostriatum following lesion of the ipsilateral nigrostriatal dopamine pathway with 1-methyl-4-phenilpyridinium ion (MPP+): reversal by embrionic nigral dopamine grafts. Mol Brain Res 9: 263–269
Tanner CM, Goetz CG, Glantz RH, Klawans HL (1982) Pergolide mesylate and idiopathic Parkinson's disease. Neurology 32: 1175–1179
Thal LJ, Sharpless NS, Hirchhorn ID, Horowitz SG, Makman MH (1983) Striatal metenkephalin concentration increases following nigrostriatal denervation. Biochem Pharmacol 32: 3297–3301
Vernier P, Julien J-F, Rataboul P, Fourrier O, Feuerstein C, Mallet J (1988) Similar time course changes in striatal levels of glutamic acid decarboxylase and proenkephalin mRNA following dopaminergic deafferentation in the rat. J Neurochem 51: 1376–1379
Voorn P, Roest G, Groeneweger HJ (1987) Increase of enkephalin and decrease of SP immunoreactivity in the dorsal and ventral striatum of the rat after midbrain 6-hydroxydopamine lesions. Brain Res 412: 391–396
Young III WS, Bonner TI, Brann MR (1986) Mesencephalic dopmaine neurons regulate the expression of neuropeptide mRNAs in the rat forebrain. Proc Natl Acad Sci 83: 9827–9831
Yoshikawa K, Williams C, Sabol SL (1984) Rat brain preproenkephalin mRNA. J Biol Chem 259: 301–308
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Granata, R., Wenning, G.K., Jolkkonen, J. et al. Effect of repeated administration of dopamine agonists on striatal neuropeptide mRNA expression in rats with a unilateral nigral 6-hydroxydopamine lesion. J. Neural Transmission 103, 249–260 (1996). https://doi.org/10.1007/BF01271237
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DOI: https://doi.org/10.1007/BF01271237