Abstract
After 10–12 weeks of chronic haloperidol administration rats with frontal cortex ablations or lesions induced by intracerebroventricular injection of 6-hydroxydopamine developed vacuous chewing behavior at a fairly stable frequency (bifrontal ablations had 15–20, 6-hydroxy-dopamine lesioned rats 7–12 chewing movements/min). This behavior persisted for 10 weeks after the last injection of haloperidol decanoate. However, rats with frontal cortex lesions developed a low rate of vacuous chewings (4–8 chewings/min) even without haloperidol administration. Bilateral intrastriatal injections of kainic acid in combination with chronic haloperidol administration did not cause chewing movements in excess of unlesioned haloperidol-treated controls.
Pharmacological tests of this animal model for tardive dyskinesia (TD) revealed similarities to human TD, but also differences. Dopamine agonists (apomorphine) and antagonists (haloperidol) both lowered chewing behavior analogous to reported effects on TD and so did gabaculine. The cholinergic drugs physostigmine and pilocarpine, however, increased chewing in rats, while anticholinergics (atropine) reduced it, in contrast to reported effects on human TD.
Similar content being viewed by others
References
Barany S., Gunne LM (1979) Pharmacological modification of experimental tardive dyskinesia. Acta Pharmacol Toxicol 45:107–111
Bédard P, Deléan J, Lafleur J, LaRochelle L (1977) Haloperidol-induced dyskinesias in the monkey. Can J Neurol Sci 4:1972
Carroll BJ, Curtis GC, Komen E (1977) Paradoxical response to dopamine agonists in tardive dyskinesia. Am J Psychiatry 134:785–789
Casey DE, Gerlach J, Magelund G, Christensen TR (1980) Gamma-acetylenic GABA in tardive dyskinesia. Arch Gen Psychiatry 37:1376–1379
Clow A, Jenner P, Marsden CD (1979) Changes in dopamine-mediated behaviour during one year's neuroleptic administration. Eur J Pharmacol 57:365–375
Clow A, Theodoruou A, Jenner P, Marsden CD (1980) A comparison of striatal and mesolimbic dopamine function in the rat during 6-month trifluoperazine administration. Psychopharmacology 69:227–233
Coyle JT, Schwarcz R (1976) Lesion of striatal neurons with kainic acid provides a model for Huntington's chorea. Nature 266:377–378
Dellow PG, Lund JP (1971) Evidence for central timing of rhythmical mastication. J Physiol 215:1–13
Fann WE, Lake CR, Gerber CJ, McKenzie GM (1974) Cholinergic suppression of tardive dyskinesia. Psychopharmacologia 37:101–107
Gerlach J, Reisby N, Randrup A (1974) Dopaminergic hypersensitivity and cholinergic hypofunction in the pathophysiology of tardive dyskinesia. Psychopharmacologia 34:21–35
Gibson CJ, Deikel SM, Young SN, Binik YM (1982) Behavioral and biochemical effects of tryptophan, tyrosine and phenylalanine in mice. Psychopharmacology 76:118–121
Glassman RB, Glassman HN (1980) Oral dyskinesia in brain-damaged rats withdrawn from a neuroleptic: implication for models of tardive dyskinesia. Psychopharmacology 69:19
Goldberg AM, McCaman RE (1973) The determination of picomole amounts of acetylcholine in mammalian brain. J Neurochem 20: 1–8
Growdon JH (1979) Choline, lecithin and tardive dyskinesia. In: Poirier LJ, Sourkes TL, Bédard PJ (eds) The extrapyramidal system and its disorders. Raven, New York, pp 387–394
Gunne LM, Barany S (1976) Haloperidol-induced tardive dyskinesia in monkeys. Psychopharmacology 50:237
Kim JS, Bak IJ, Hassler R, Okada Y (1971) Role of γ-aminobutyric acid (GABA) in the extrapyramidal motor system. II. Some evidence for the existence of a type of GABA-rich strio-nigral neurons. Exp Brain Res 14:95–104
Kirk RE (1968) Experimental design: Procedures for the behavioral sciences. Brooks/Cole Publishing Company, Belmont, California
Klawans HL, Rubovits R (1974) Effect of cholinergic and anticholinergic agents on tardive dyskinesia. J Neurol Neurosurg Psychiatry 37:941–947
König JFR, Klippel RA (1963) The rat brain. A stereotaxic atlas of the forebrain and lower parts of the brain stem. The Williams and Wilkins Co, Baltimore
McGeer EG, McGeer PL, Hattori T, Vincent CR (1979) Kainic acid, neurotoxicity and Huntington's disease. In: Chase TN, Wexler N, Barbeau A (eds) Huntington's disease. Raven, New York, pp 577–591
Noble EP, Wurtman RJ, Axelrod J (1967) A simple and rapid method for injecting H3-norepinephrine into the lateral ventricle of the rat brain. Life Sci 6:281–291
Palfreyman MG, Robin MM, Zraika M, Gardner CR, Schechter PJ (1980) Dyskinesia induced by intracerebral injections of GABA-T inhibitors: A striatal or cortical phenomenon. Brain Res Bull 5 [Suppl 2]:613–619
Smith RC, Tamminga CA, Haraszti J, Pandey GN, Davis JM (1977) Effects, of dopamine agonists in tardive dyskinesia. Am J Psychiatry 134:763–768
Snyder SH (1981) Dopamine receptors, neuroleptics, and schizophrenia. Am J Psychiatry 138:460–464
Tamminga CA, Smith RC, Ericksen SE, Chang S, Davis JM (1977) Cholinergic influences in tardive dyskinesia. Am J Psychiatry 134:769–774
Tamminga CA, Caryton JW, Chase TN (1979) Improvement in tardive dyskinesia after muscimol therapy. Arch Gen Psychiatry 36:595–598
Tarsy D, Baldessarini RJ (1974) Behavioural supersensitivity to apomorphine following chronic treatment with drugs which interfere with the synaptic functions of catecholamines. Neuropharmacology 13:927–940
Tolosa E (1978) Modification of tardive dyskinesia and spasmodic torticollis by apomorphine. Arch Neurol 35:459–462
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Gunne, L.M., Growdon, J. & Glaeser, B. Oral dyskinesia in rats following brain lesions and neuroleptic drug administration. Psychopharmacology 77, 134–139 (1982). https://doi.org/10.1007/BF00431935
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00431935