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Effects of dopamine agonists, catecholamine depletors, and cholinergic and GABAergic drugs on acute dyskinesias in squirrel monkeys

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Abstract

It has been suggested that the neuroleptic-induced acute dyskinetic syndrome in monkeys may be a useful model of extrapyramidal dysfunction. Various drugs that have well-characterized effects on clinical extrapyramidal syndromes and on catecholaminergic, cholinergic, or GABAergic neurotransmission were assessed in dyskinesia-susceptible squirrel monkeys. Catecholamine depletors (α-methyl-p-tyrosine, tetrabenazine) induced the syndrome, as do dopamine (DA) receptor antagonists, and d-amphetamine reversed the effects of tetrabenazine. The haloperidol-induced syndrome was reversed by the indirectly acting DA agonists amantadine and L-dopa. Neither of the DA autoreceptor agonists TL-99 or 3-PPP elicited this syndrome, suggesting that these agents lack extrapyramidal involvement. Anticholinergics reversed haloperidol-induced dyskinesias and the cholinomimetic arecoline was capable of inducing dyskinesias. When coadministered repeatedly with haloperidol, benztropine suppressed the emergence of susceptibility to neuroleptic-induced dyskinesias. These results confirm that the acute dyskinetic syndrome in the monkey is characterized by DA deficiency and acetylcholine excess. Diazepam and baclofen, which have been reported to have some clinical benefit in tardive dyskinesia, suppressed haloperidol-induced acute dyskinesias without causing gross motor depression. Pharmacological manipulation of GABAergic pathways from striatum may constitute a fruitful approach to the treatment of dyskinetic motor disorders.

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References

  • Allen RM (1982) Palliative treatment of tardive dyskinesia with combination of amantadine-neuroleptic administration. Biol Psychiatry 17:719–727

    Google Scholar 

  • Asher SW, Aminoff MJ (1981) Tetrabenazine and movement disorders. Neurology 31:1051–1054

    Google Scholar 

  • Barany S, Anders I, Gunne LM (1979) Development of acute dystonia and tardive dyskinesia in Cebus monkeys. Res Commun Chem Pathol Pharmacol 25:269–279

    Google Scholar 

  • Bedard P, Delean J, Lafleur J, Larochelle L (1977) Haloperidol-induced dyskinesias in the monkey. Can J Neurol Sci 4:197–201

    Google Scholar 

  • Bianchine JR (1980) Drugs for Parkinson's disease: Centrally acting muscle relaxants. In: Gilman AG, Goodman LS, Gilman A (eds) The pharmacological basis of therapeutics. MacMillan, New York, pp 475–493

    Google Scholar 

  • Carey RJ, DeVeaugh-Geiss J (1982) Chronic benztropine and haloperidol administration induce behaviorally equivalent pharmacological hypersensitivities separately but not in combination. Psychopharmacology 76:341–345

    Google Scholar 

  • Casey DE, Gerlach J, Christensson E (1980) Dopamine, acetylcholine, and GABA effects in acute dystonia in primates. Psychopharmacology 70:83–87

    Google Scholar 

  • Clark D, Carlsson A, Hjorth S, Svensson K, Engel J, Sanchez D (1982) Is 3-PPP a potential antipsychotic agent? Evidence from animal behavioural studies. Eur J Pharmacol 83:131–134

    Google Scholar 

  • Costa E, Guidotti A (1979) Molecular mechanisms in the receptor action of benzodiazepines. Annu Rev Pharmacol Toxicol (Copenh) 19:531–545

    Google Scholar 

  • Dill RE, Jones DL, Gillin JC, Murphy G (1979) Comparison of behavioral effects of systemic L-dopa and intracranial dopamine in mesolimbic forebrain of nonhuman primates. Pharmacol Biochem Behav 10:711–716

    Google Scholar 

  • DiMascio A, Bernardo DL, Greenblatt DJ, Marder JE (1976) A controlled trial of amantadine in drug-induced extrapyramidal disorders. Arch Gen Psychiatry 33:599–602

    Google Scholar 

  • Director KL, Muniz CE (1982) Diazepam in the treatment of extrapyramidal symptoms: A case report. J Clin Psychiatry 43:160–161

    Google Scholar 

  • Fenton HM, Hall NR, Gerhardt S, Noreika L, Neale R, Liebman JM (1983) Avoidance and ICSS behavioral models dissociate TL-99 and 3-PPP from dopamine receptor antagonists. Eur J Pharmacol 91:421–430

    Google Scholar 

  • Forchetti C, Scarnati E, Pacitti C, Agnoli A (1980) Striatal cholinergic receptors and dyskinetic motor activity in the rat. Neurosci Lett 20:363–367

    Google Scholar 

  • Freedman R, Kirch D, Bell J, Adler LE, Pecevich M, Pachtman E, Denver P (1982) Glonidine treatment of schizophrenia: Doubleblind comparison to placebo and neuroleptic drugs. Acta Psychiatr Scand 65:34–45

    Google Scholar 

  • Gerlach J, Rye T, Kristjansen P (1978) Effect of baclofen on tardive dyskinesia. Psychopharmacology 56:145–151

    Google Scholar 

  • Giarman NJ, Roth RH (1964) Differential estimation of γ-butyrolactone and γ-hydroxybutyric acid in rat blood and brain. Science 145:583–584

    Google Scholar 

  • Goetz CG, Weiner WJ, Nausieda PA, Klawans HL (1982) Tardive dyskinesia: Pharmacology and clinical implications. Clin Neuropharmacol 5:3–22

    Google Scholar 

  • Goodale DB, Rusterholz DB, Long JP, Flynn JR, Walsh B, Cannon JG, Lee T (1980) Neurochemical and behavioral evidence for a selective presynaptic dopamine receptor agonist. Science 210:1141–1143

    Google Scholar 

  • Hill DR, Bowery NG (1981) 3H-Baclofen and 3H-GABA bind to bicuculline-insensitive GABA-B sites in rat brain. Nature 290:149–152

    Google Scholar 

  • Hjorth S, Carlsson A, Wikstrom H, Lindberg P, Sanchez D, Hacksell U, Arvidsson LE, Svensson U, Nilsson JLG (1981) 3-PPP: A new centrally acting DA-receptor agonist with selectivity for autoreceptors. Life Sci 28:1225–1238

    Google Scholar 

  • Jeste DV, Wyatt RJ (1982) Therapeutic strategies against tardive dyskinesia. Arch Gen Psychiatry 39:803–816

    Google Scholar 

  • Jus K, Jus A, Gautier J, Villeneuve A, Pires P, Pineau R, Villeneuve R (1974) Studies on the action of certain pharmacological agents on tardive dyskinesia and on the rabbit syndrome. Int J Clin Pharmacol 9:138–145

    Google Scholar 

  • Kitzen JM, Long JP, Cannon JG (1978) Pharmacology of 6,7-dihydroxy-2-dimethylaminotetralin (TL-99). I. Cardiovascular activity in the dog and cat. J Pharmacol Exp Ther 206:239–247

    Google Scholar 

  • Liebman J, Neale R (1980) Neuroleptic-induced acute dyskinesias in squirrel monkeys: Correlation with propensity to cause extrapyramidal side effects. Psychopharmacology 68:25–29

    Google Scholar 

  • Liebman JM, Neale R, Noreika L, Braunwalder A (1981) Differential reversal of various dopamine antagonists by anticholinergics in Sidman avoidance: Possible relationship to adrenergic blockade. Psychopharmacology 75:248–253

    Google Scholar 

  • Login IS, Cronin MJ, MacLeod RM (1982) Tetrabenazine has properties of a dopamine receptor antagonist. Ann Neurol 12:257–262

    Google Scholar 

  • Lundh H, Tunving K (1981) An extrapyramidal choreiform syndrome caused by amphetamine addiction. J Neurol Neurosurg Psychiatry 44:728–730

    Google Scholar 

  • Magelund G, Gerlach J, Casey DE (1979) Neuroleptic-potentiating effect of α-methyl-p-tyrosine compared with haloperidol and placebo in a double-blind cross-over trial. Acta Psychiatr Scand 60:185–189

    Google Scholar 

  • Marsden CD, Jenner P (1980) The pathophysiology of extrapyramidal side effects of neuroleptic drugs. Psychol Med 10:55–72

    Google Scholar 

  • Marsden CD, Sheehy MP (1981) GABA and movement disorders. In: DiChiara G, Gessa GL (eds) GABA and the basal ganglia. Raven, New York, pp 225–234

    Google Scholar 

  • Meldrum DS, Anlezark GM, Marsden CD (1977) Acute dystonia as an idiosyncratic response to neuroleptics in baboons. Brain 100:313–326

    Google Scholar 

  • Murphy DL, Dill RE (1972) Chemical stimulation of discrete brain loci as a method of producing dyskinesia models in primates. Exp Neurol 34:244–254

    Google Scholar 

  • Neale R, Gerhardt S, Fallon S, Liebman JM (1982) Progressive changes in the acute dyskinetic syndrome as a function of repeated elicitation in squirrel monkeys. Psychopharmacology 77:223–228

    Google Scholar 

  • Neale R, Gerhardt S, Liebman JM (1983) Effects of the novel antipsychotics, RMI-81582 and clopipazan on predictors of extrapyramidal liability in squirrel monkeys. Drug Dev Res 3:171–176

    Google Scholar 

  • Peroutka SJ, Snyder SH (1980) Relationship of neuroleptic drug effects at brain dopamine, serotonin, α-adrenergic, and histamine receptors to clinical potency. Am J Psychiatry 137:1518–1522

    Google Scholar 

  • Porsolt RD, Jalfre M (1981) Neuroleptic-induced acute dyskinesias in rhesus monkeys. Psychopharmacology 75:16–21

    Google Scholar 

  • Schulz SC, van Kammen DP, Buchsbaum MS, Roth RH, Alexander P, Bunney Jr WE (1981) γ-Hydroxybutyrate treatment of schizophrenia: A pilot study. Pharmacopsychiatry 14:129–134

    Google Scholar 

  • Stahl SM, Davis KL, Berger PA (1982) The neuropharmacology of tardive dyskinesia, spontaneous dyskinesia, and other dystonias. J Clin Psychopharmacol 2:321–328

    Google Scholar 

  • Stockhausen FG (1960) Clinical studies with tetrabenazine (RO 1-9569). Dis Nerv Syst 21:115–117

    Google Scholar 

  • Weiner WJ, Bergen D (1977) Prevention and management of the side effects of levodopa. Clin Neuropharmacol 2:1–23

    Google Scholar 

  • Weiss B, Santelli S, Lusink G (1977) Movement disorders induced in monkeys by chronic haloperidol treatment. Psychopharmacology 3:289–293

    Google Scholar 

  • Wilbur R, Kulik FA (1981) Propranolol (Inderal) for tardive dyskinesia and extrapyramidal side effects from neuroleptics: Possible involvement of beta-adrenergic mechanisms. Prog Neurol Psychopharmacol 4:627–632

    Google Scholar 

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Authors and Affiliations

  1. Research and Development Department, Pharmaceuticals Division, CIBA-Geigy Corporation, 07901, Summit, NJ, USA

    Robert Neale, Susan Gerhardt & Jeffrey M. Liebman

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  1. Robert Neale
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  2. Susan Gerhardt
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  3. Jeffrey M. Liebman
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Neale, R., Gerhardt, S. & Liebman, J.M. Effects of dopamine agonists, catecholamine depletors, and cholinergic and GABAergic drugs on acute dyskinesias in squirrel monkeys. Psychopharmacology 82, 20–26 (1983). https://doi.org/10.1007/BF00426374

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  • DOI: https://doi.org/10.1007/BF00426374

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