Skip to main content
Log in

Chronic neuroleptics alter the effects of the D1 agonist SK&F 38393 and the D2 agonist LY171555 on oral movements in rats

  • Original Investigations
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Vacuous oral movements (OMs) in rats chronically administered haloperidol (HAL), fluphenazine (FLU), or no drug were studied following injections of one of three doses of either a D1 agonist (SK&F 38393) or a D2 agonist (LY171555). Oral movements were observed via closed-circuit television and simultaneously recorded using a computerized video analysis system which measured the distance between two fluorescent dots painted above and below the rat's mouth. SK&F 38393 induced a dose-dependent increase in tremorous oral movements and repetitive chewing movements in the controls; this effect was more pronounced in rats treated with chronic HAL or FLU, both during chronic neuroleptic treatment and even more so when they were tested after drug withdrawal following 5 or 14 months of chronic neuroleptic administration. Conversely, LY171555 produced an inhibition of oral activity at all dose levels in controls. This inhibition was attenuated during chronic administration of HAL or FLU, but returned to control levels (without any signs of supersensitivity) when the animals were retested shortly after discontinuation of neuroleptics. These results indicate that heightened oral movements in rodents following chronic neuroleptic administration can be more clearly induced by D1 than by D2 receptor activation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Altar C, Boyar W, Wood P (1987) Dopamine autoreceptor agonists including CGS 15855A decrease dopamine release and metabolism in mouse brain. Eur J Pharmacol 134:303–311

    Google Scholar 

  • Burt DR, Creese I, Snyder SH (1977) Antischizophrenic drugs: chronic treatment elevates dopamine receptor binding in brain. Science 196:326–328

    Google Scholar 

  • Creese I (1983) Receptor interactions of neuroleptics. In: Coyle J, Enna S (eds) Neuroleptics: neurochemical, behavioral, and clinical perspectives. Raven Press, New York, pp 183–223

    Google Scholar 

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

    Google Scholar 

  • Fibiger HC, Lloyd KD (1984) Neurobiological substrates of tardive dyskinesia: the GABA hypothesis. Trends Neurosci 8:462–464

    Google Scholar 

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

    Google Scholar 

  • Hyttel J, Larsen J, Christensen A, Arnt J (1985) Receptor-binding profiles of neuroleptics. In: Casey D, Chase T, Christensen A, Gerlach J (eds) Dyskinesia, research and treatment. Psychopharmacology [Suppl] 2:9–18

    Google Scholar 

  • Johansson P, Levin E, Gunne L, Ellison G (1987) Opposite effects of a D1 and a D2 agonist on oral movements in rats. Eur J Pharmacol 134:83–88

    Google Scholar 

  • Kebabian JW, Calne DB (1979) Multiple receptors for dopamine. Nature 277:93–96

    Google Scholar 

  • Klawans HL (1973) The pharmacology of tardive dyskinesias. Am J Psychiatry 130:82–86

    Google Scholar 

  • Memo M, Pizzi M, Missale C, Carruba M, Spano P (1987) Modification of the function of D1 and D2 dopamine receptors in striatum and nucleus accumbens of rats chronically treated with haloperidol. Neuropharmacology 26:477–480

    Google Scholar 

  • Molloy A, Waddington J (1984) Dopaminergic behavior 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 

  • Rosengarten H, Schweitzer J, Friedhoff A (1983) Induction of oral dyskinesias in naive rats by D1 stimulation. Life Sci 33:2479–2482

    Google Scholar 

  • Rosengarten H, Schweitzer J, Friedhoff A (1986) Selective dopamine D2 receptor reduction enhances a D1 mediated oral dyskinesia in rats. Life Sci 39:29–35

    Google Scholar 

  • Sant WW, Ellison G (1984) Drug holidays alter onset of oral movements in rats following chronic haloperidol. Biol Psychiatry 19:95–99

    Google Scholar 

  • Snyder S (1981) Dopamine receptors, neuroleptics, and schizophrenia. Am J Psychiatry 138:460–464

    Google Scholar 

  • Stoof J, Kebabian J (1981) Opposing roles for D1 and D2 dopamine receptors in efflux of cyclic AMP from rat neurostriatum. Nature 294:366–368

    Google Scholar 

  • Strombom U (1976) Catecholamine receptor agonists effects on motor activity and route of tyrosine hydroxylation in mouse brain. Naunyn-Schmiedeberg's Arch Pharmacol 292:167–174

    Google Scholar 

  • Waddington JL (1984) Tardive dyskinesia: a critical re-evaluation of the causal role of neuroleptics and of the dopamine receptor supersensitivity hypothesis. In: Callaghan N, Galvin R (eds) Recent research in neurology. Pitman, London, pp 34–48

    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

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ellison, G., Johansson, P., Levin, E. et al. Chronic neuroleptics alter the effects of the D1 agonist SK&F 38393 and the D2 agonist LY171555 on oral movements in rats. Psychopharmacology 96, 253–257 (1988). https://doi.org/10.1007/BF00177570

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00177570

Key words

Navigation