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Relationship of orofacial movements to behavioural repertoire as assessed topographically over the course of 6-month haloperidol treatment followed by 4-month withdrawal

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Abstract

Rationale

Late-onset vacuous chewing movements (VCMs) arise in a significant proportion of rats treated chronically with conventional antipsychotic drugs. Given their common action to block dopamine D2-like receptors, VCMs may be related to changes in dopaminergic function; if so, other typical dopamine-mediated behaviours might be altered also.

Objective

To examine this hypothesis, behavioural repertoire was studied topographically over the course of chronic treatment and withdrawal.

Methods

Animals were injected with haloperidol decanoate 28 mg/kg IM, or vehicle, every 3 weeks for 27 weeks, and then maintained without treatment for a further 18 weeks. Immediately before each injection and during withdrawal, VCMs and other topographies of behaviour were assessed.

Results

In both control and haloperidol-treated rats, exploratory behaviours declined over the study, indicating habituation effects. Conversely, VCMs emerged after 6 weeks of treatment with haloperidol and persisted after withdrawal; VCM and locomotion were not related, indicating that in treated rats, increased VCMs are not an artifact of reduced locomotion. Treated animals with VCMs evidenced increases in buccal tremor and grooming behaviour relative to those without VCMs, although no clear relationship to the emergence of VCMs was established; there were no material differences in any other topographies of behaviour.

Conclusion

The effect of long-term treatment with haloperidol to induce VCMs is not reflected in fundamental changes in dopamine-mediated behavioural topography but, rather, appears to affect neural mechanisms involved in orofacial movement preferentially.

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References

  • Andreassen OA, Jørgensen HA (1995) The rat model of tardive dyskinesia: relationship between vacuous chewing movements and gross motor activity during acute and long-term haloperidol treatment. Life Sci 57:2263–2272

    Article  CAS  PubMed  Google Scholar 

  • Andreassen OA, Finsen B, Ostergaard K, Sorensen JC, West MJ, Jørgensen HA (1999) The relationship between oral dyskinesias produced by long-term haloperidol treatment, the density of striatal preproenkephalin messenger RNA and enkephalin peptide, and the number of striatal neurons expressing preproenkephalin messenger RNA in rats. Neuroscience 88:27–35

    Google Scholar 

  • Bernardi MM, Neto JP (1979) Effects of abrupt and gradual withdrawal from long-term haloperidol treatment on open field behaviour of rats. Psychopharmacology 65:247–250

    CAS  PubMed  Google Scholar 

  • Clifford JJ, Waddington JL (1998) Heterogeneity of behavioural profile between three new putative selective D3 dopamine receptor antagonists using an ethologically based approach. Psychopharmacology 136:284–290

    CAS  PubMed  Google Scholar 

  • Clifford JJ, Waddington JL (2000) Topographically based search for an 'ethogram' among a series of novel D4 dopamine receptor agonists and antagonists. Neuropsychopharmacology 22:538–544

    Article  CAS  PubMed  Google Scholar 

  • Deveney AM, Waddington JL (1995) Pharmacological characterisation of behavioural responses to SK&F 83959 in relation to D1-like dopamine receptors not linked to adenylyl cyclase. Brit J Pharmacol 116:2120–2126

    CAS  Google Scholar 

  • Egan MF, Hurd Y, Hyde TM, Weinberger DR, Wyatt RJ, Kleinman JE (1994) Alterations in dopamine receptor and neuropeptide gene expression in striatonigral and striatopallidal neurons in rats with vacuous chewing movements induced by chronic treatment with haloperidol. Synapse 18:178–189

    CAS  PubMed  Google Scholar 

  • Egan MF, Ferguson J, Hyde TM (1996a) Effects of rating parameters on assessment of neuroleptic-induced vacuous chewing movements. Pharmacol Biochem Behav 53:401–410

    Article  CAS  PubMed  Google Scholar 

  • Egan MF, Hurd Y, Ferguson J, Bachus SE, Hamid EH, Hyde TM (1996b) Pharmacological and neurochemical differences between acute and tardive vacuous chewing movements induced by haloperidol. Psychopharmacology 127:337–345

    Google Scholar 

  • Ellison E, See RE (1989) Rats administered chronic neuroleptics develop oral movements which are similar in form to those in humans with tardive dyskinesia. Psychopharmacology 98:564–566

    Google Scholar 

  • Ellison E, See RE (1990) Chronic administration of typical, but not atypical neuroleptics induce persisting alterations in rest-activity cycles in rats. Pharmacol Biochem Behav 36:807–811

    Article  CAS  PubMed  Google Scholar 

  • Ellison E, See RE, Levin E, Kinney J (1987) Tremorous mouth movements in rats administered chronic neuroleptics. Psychopharmacology 92:122–126

    CAS  PubMed  Google Scholar 

  • Glassman RB, Glassman HN (1980) Oral dyskinesia in brain-damaged rats withdrawn from neuroleptic: implication for models of tardive dyskinesia. Psychopharmacology 69:19–25

    CAS  PubMed  Google Scholar 

  • Gunne LM, Haggstrom J-E (1983) Reduction in nigral glutamic acid decarboxylase in rats with neuroleptic-induced oral dyskinesia. Psychopharmacology 81:191–194

    CAS  PubMed  Google Scholar 

  • Jicha G, Salamone JD (1991) Vacuous jaw movements and feeding deficits in rats with ventrolateral striatal dopamine depletions: possible model of parkinsonian symptoms. J Neurosci 11:3822–3829

    CAS  PubMed  Google Scholar 

  • Jørgensen HA, Andreassen OA, Hole K (1994) The relationship between motor effects in rats following acute and chronic haloperidol treatment. Psychopharmacology 116:89–92

    Google Scholar 

  • Kane JM (1992) Tardive dyskinesia. American Psychiatric Association, Washington, DC

  • Levy AD, See RD, Levin ED, Ellison GD (1987) Neuroleptic-induced oral movements in rats: methodological issues. Life Sci 41:1499–1506

    Article  CAS  PubMed  Google Scholar 

  • Meredith GE, DeSouza IAJ, Hyde TM, Tipper G, Wong ML, Egan MF (2000) Persistent alterations in dendrites, spines and dynorphinergic synapses in the nucleus accumbens shell of rats with neuroleptic-induced dyskinesias. J Neurosci 20:7798–7806

    CAS  PubMed  Google Scholar 

  • Molloy AM, Waddington JL (1984) Dopaminergic behaviour stereospecifically promoted by the D-1 agonist R-SK&F 38393 and selectively blocked by the D-1 antagonist SCH 23390. Psychopharmacology 82:409–410

    Google Scholar 

  • Niznik HB, Sugamori KS, Clifford JJ, Waddington JL (2002) D1-like dopamine receptors: molecular biology and psychopharmacology. In: Di Chiara G (ed) Handbook of pharmacology: dopamine in the CNS. Springer, Berlin Heidelberg New York, pp 121–158

  • Rosengarten H, Schwietzer JW, Friedhoff AJ (1983) Induction of oral dyskinesia in naïve rats by D-1 stimulation. Life Sci 33:2479–2482

    Article  CAS  PubMed  Google Scholar 

  • Rosengarten H, Friedhoff AJ (1998) A phosphoinositide-linked dopamine D1 receptor mediates repetitive jaw movements in rats. Biol Psychiat 44:1178–1184

    Article  CAS  PubMed  Google Scholar 

  • Rupniak NMJ, Jenner P, Marsden CD (1985) Pharmacological characterization of spontaneous or drug-induced purposeless chewing movements in rats. Psychopharmacology 85:71–79

    Google Scholar 

  • Rupniak NMJ, Jenner P, Marsden CD (1986) Acute dystonia induced by neuroleptic drugs. Psychopharmacology 88:403–419

    Google Scholar 

  • Salamone JD, Mayorga AJ, Trevitt JT, Cousins MS, Conlan A, Nawab A (1998) Tremulous jaw movements in rats: a model of parkinsonian tremor. Prog Neurobiol 56:591–611

    CAS  PubMed  Google Scholar 

  • Seeman P (1992) Dopamine receptor sequences: therapeutic levels of neuroleptics occupy D2 receptors, clozapine occupies D4. Neuropsychopharmacology 7:261–284

    Google Scholar 

  • Steinpreis RE, Salamone JD (1993) The effects of acute haloperidol and reserpine administration on vacuous chewing movements in three age groups of rats. Pharm Biochem Behav 46:405–409

    Article  CAS  Google Scholar 

  • Steinpreis RE, Baskin PP, Salamone JD (1993) Vacuous jaw movements induced by sub-chronic administration of haloperidol: interactions with scopolamine. Psychopharmacology 111:99–105

    Google Scholar 

  • Tamminga CA, Dale JM, Goodman L, Kaneda H, Kaneda N (1990) Neuroleptic-induced vacuous chewing movements as an animal model of tardive dyskinesia: a study in three rat strains. Psychopharmacology 102:474–478

    Google Scholar 

  • Waddington JL (1989) Schizophrenia, affective psychoses and other disorders treated with neuroleptic drugs: the enigma of tardive dyskinesia, its neurobiological determinants, and the conflict of paradigms. Int Rev Neurobiol 31:297–353

    CAS  PubMed  Google Scholar 

  • Waddington JL (1990) Spontaneous orofacial movements induced in rodents by very long-term neuroleptic administration: Phenomenology, pathophysiology and putative relationship to tardive dyskinesia. Psychopharmacology 101:431–447

    CAS  PubMed  Google Scholar 

  • Waddington JL (1997) Rodent and other animal models of tardive dyskinesia during long-term neuroleptic drug administration: controversies and implications for the clinical syndrome. In: Yassa R, Nair NPV, Jeste DV (eds) Neuroleptic-induced movement disorders. Cambridge University Press, New York, pp 225–237

  • Waddington JL, Gamble SJ (1981) Prolonged dopamine receptor blockade in rats after termination of long-term depot fluphenazine. Lancet 1:1375–1376

    CAS  PubMed  Google Scholar 

  • Waddington JL, Cross AJ, Gamble SJ, Bourne RC (1983) Spontaneous orofacial dyskinesia and dopaminergic function in rats after 6 months of neuroleptic treatment. Science 220:530–532

    CAS  PubMed  Google Scholar 

  • Waddington JL, Molloy AG, O'Boyle KM, Youssef HA (1985) Spontaneous and drug-induced dyskinesias in rodents in relation to ageing and long-term neuroleptic treatment: relationship to tardive dyskinesia. In: Shagass C, Josiassen RC, Bridger W, Weiss K, Stoff D, Simpson GM (eds) Biological psychiatry. Elsevier, New York, pp 1151–1153

  • Waddington JL, Daly SA, Downes RP, Deveney AM, McCauley PG, O'Boyle KM (1995) Behavioural pharmacology of D-1-like dopamine receptors: further subtyping, new pharmacological probes and interactions with D-2-like receptors. Prog Neuro-Psychopharmacol Biol Psychiat 19:811–831

    Google Scholar 

Download references

Acknowledgements

The authors wish to thank Dr. R. Conroy for statistical advice and C. Lyons for technical assistance. These studies were supported by Enterprise Ireland, a Galen Fellowship from the Irish Brain Research Foundation, the HEA, and the Research Committee of the Royal College of Surgeons in Ireland.

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Authors and Affiliations

  1. Department of Anatomy, Royal College of Surgeons in Ireland, St. Stephen's Green, Dublin 2, Ireland

    Ian E. J. De Souza

  2. Department of Zoology, Trinity College, Dublin 2, Ireland

    Ian E. J. De Souza & Gloria E. Meredith

  3. Department of Human Anatomy & Physiology, University College Dublin, Earlsfort Terrace, Dublin 2, Ireland

    Niamh M. Dawson

  4. Department of Clinical Pharmacology, Royal College of Surgeons in Ireland, St. Stephen's Green, Dublin 2, Ireland

    Jeremiah J. Clifford & John L. Waddington

  5. Department of Cellular and Molecular Pharmacology, Chicago Medical School, Finch University of Health Sciences, 3333 Green Bay Road, North Chicago, Il 60064, USA

    Gloria E. Meredith

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  1. Ian E. J. De Souza
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  2. Niamh M. Dawson
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  3. Jeremiah J. Clifford
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  4. John L. Waddington
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  5. Gloria E. Meredith
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Correspondence to Gloria E. Meredith.

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De Souza, I.E.J., Dawson, N.M., Clifford, J.J. et al. Relationship of orofacial movements to behavioural repertoire as assessed topographically over the course of 6-month haloperidol treatment followed by 4-month withdrawal. Psychopharmacology 169, 28–34 (2003). https://doi.org/10.1007/s00213-003-1466-2

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