Skip to main content
SpringerLink
Log in

GABA agonists in cebus monkeys with neuroleptic-induced persistent dyskinesias

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

Abstract

Tetrahydroisoxazolopyridinol (THIP), a GABA receptor agonist, γ-acetylenic-GABA(GAG) and γ-vinyl-GABA(GVG), two GABA transaminase inhibitors were given in single parenteral doses to three Cebus apella monkeys with persistent dyskinetic movements induced by earlier long-term administration of haloperidol. High doses of THIP temporarily abolished dyskinesias but also caused bradykinesia, ataxia, dystonia and myoclonic jerks. GAG and GVG reduced dyskinesias to a lesser extent and with fewer side effects. Whether the observed antidyskinetic effect is secondary to the concomitant general toxic effects or if these drugs have a specific antidyskinetic action remains an open question.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Arnt J, Scheel-Krüger J, Christensen A (1978) Development of new animal models for detecting GABAergic activity: studies with THIP and muscimol. Proc 7th Int Congr of pharmacology, Paris, abstract 1300

  • Barany S (1983) A primate model for acute dystonia and tardive dyskinesia. Development, validation and application. Acta Universitatis Upsaliensis. Abstract of Uppsala Dissertations from the Faculty of Medicine, 461

  • Björndal N, Gerlach J, Casey DE, Christensson E (1983) Effect of apomorphine and gabaergic drugs in monkeys pretreated with haloperidol. Psychopharmacology 79:220–225

    Google Scholar 

  • Bohlen P, Huot S, Palfreyman M (1979) The relationship between GABA concentrations in brain and cerebrospinal fluid. Brain Res 167:297–305

    Google Scholar 

  • Casey DE, Denney D (1977) Pharmacological characterization of tardive dyskinesia. Psychopharmacology 54:1–8

    Google Scholar 

  • Casey DE, Gerlach J, Magelund G, Christensen TR (1980) γ-acetylenic GABA in tardive dyskinesia. Arch Gen Psychiatry 37:1376–1379

    Google Scholar 

  • Ferkany J, Butler J, Enna S (1979) Effects of drugs on rat brain, cerebrospinal fluid and blood GABA content. J Neurochem 33:29–33

    Google Scholar 

  • Fibiger HC, Lloyd KG (1984) Neurobiological substrates of tardive dyskinesia: the GABA hypothesis. TINS 7:462–464

    Google Scholar 

  • Gale K, Casu M (1981) Dynamic utilization of GABA in substantia nigra: regulation by dopamine and GABA in the striatum, and its clinical and behavioral implications. Mol Cell Biochem 39:369–405

    Google Scholar 

  • Gerlach J, Reisby N, Randrup A (1974) Dopaminergic hypersensitivity and cholinergic hypofunction in the pathophysiology of tardive dyskinesia. Psychopharmacology 34:21–35

    Google Scholar 

  • Grove J, Schechter P, Tell G, Koch-Weser J, Sjoerdsma A, Warter J, Marescaux C, Rumbach L (1981) Increased gamma-aminobutyric acid (GABA), homocarnosine and beta-alanine in cerebrospinal fluid of patients treated with gamma-vinyl GABA. Life Sci 28:2431–2439

    Google Scholar 

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

    Google Scholar 

  • Gunne LM, Häggström J-E, Sjöqvist B (1984) Association with persistent neuroleptic-induced dyskinesia of regional changes in brain GABA synthesis. Nature 309:347–349

    Google Scholar 

  • Häggström J-E (1984) Effects of sulpiride on persistent neuroleptic-induced dyskinesia in monkeys. Acta Psychiatr Scand [Suppl] 69:103–108

    Google Scholar 

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

    Google Scholar 

  • Jung M, Lippert B, Metcalf B, Schechter P, Sjoerdsma A (1977a) The effect of 4-amino-hex-5-ynoic acid (gamma-acetylenic GABA, gamma-ethynul GABA), a catalytic inhibitor of GABA metabolism in vivo. J Neurochem 28:717–723

    Google Scholar 

  • Jung MJ, Lippert BW, Metcalf P, Böhlen P, Schechter PJ (1977b) γ-vinyl GABA (4-amino-hex-5-ynoic acid), a new selective irreversible inhibitor of GABA-T: effects on brain GABA metabolism in mice. J Neurochem 29:797–802

    Google Scholar 

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

    Google Scholar 

  • Korsgaard S, Casey D, Gerlach J, Hertmar O, Kaldan B, Mikkelsen L (1982) The effect of tetrahydroisoxazolopyridinol (THIP) in tardive dyskinesia. Arch Gen Psychiatry 39:1017–1021

    Google Scholar 

  • Korsgaard S, Casey DE, Gerlach J (1983) Effect of gamma-vinyl GABA in tardive dyskinesia. Psychiatr Res 8:261–269

    Google Scholar 

  • Löscher W (1979) GABA in plasma and cerebrospinal fluid of different species. Effects of gamma-acetylenic GABA, gamma-vinyl GABA and sodium valproate. J Neurochem 32:1587–1591

    Google Scholar 

  • Meldrum B, Horton R (1980) Effects of the bicyclic GABA agonist, THIP, on myoclonic and seizure responses in mice and baboons with reflex epilepsi. Eur J Pharmacol 61:231–237

    Google Scholar 

  • Metcalf B, Jung M, Lippert B, Casara P, Bohlen P, Schechter P (1979) Gamma-acetylenic-GABA and gamma-vinyl-GABA - two enzyme activated irreversible inhibitors of GABA aminotransferase. In: Krogsgaard-Larsen, Scheel-Krüger, Kofod (eds). GABA neurotransmittors. Munksgaard, Copenhagen, pp 236–246

    Google Scholar 

  • Palfreyman M, Huot S, Lippert B, Schechter P (1978) The effect of gamma-acetylenic GABA, and enzyme-activated irreversible inhibitor of GABA-transaminase, on dopamine pathways of the extrapyramidal and limbic systems. Eur J Pharmacol 50:325–336

    Google Scholar 

  • Scheel-Krüger J, Arnt J, Magelund G (1977) Behavioral stimulation induced by muscimol and other GABA agonists injected into the substantia nigra. Neurosci Lett 4:351–356

    Google Scholar 

  • Schou F, Iversen LL (1974) The use of autoradiographic techniques for the identification and mapping of transmittor-specific neurons in the brain. Life Sci 15:157–175

    Google Scholar 

  • Stahl SM, Thornton JE, Simpson ML, Berger PA, Napoliello MJ (1985) Gamma-vinyl-GABA treatment of tardive dyskinesia an other movement disorders. Biol Psychiatry 20:888–893

    Google Scholar 

  • Tamminga CA, Thaker GK, Ferraro TN, Hare TA (1983) GABA agonist treatment improves tardive dyskinesia. Lancet II:97–98

    Google Scholar 

  • Tell GP, Schechter PJ, Koch-Weser J, Cantinaux P, Chabannes JP, Lambert PA (1981) Effects of γ-vinyl GABA. N Engl J Med 305:581–589

    Google Scholar 

  • Thaker GK, Tamminga GK, Alphs LD, Lafterman J, Ferraro TN, Hare TA (1987) Brain γ-aminobutyric acid. Abnormality in tardive dyskinesia. Arch Gen Psychiatry 44:522–529

    Google Scholar 

  • Waszczak B, Hruska K, Walters J (1980) GABAergic actions of THIP in vivo and in vitro: a comparison with muscimol and GABA. Eur J Pharmacol 65:21–29

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Psychiatric Research Center, University of Uppsala, S-750 17, Uppsala, Sweden

    Ulf Andersson & Jan-Erik Häggström

Authors
  1. Ulf Andersson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jan-Erik Häggström
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Andersson, U., Häggström, JE. GABA agonists in cebus monkeys with neuroleptic-induced persistent dyskinesias. Psychopharmacology 94, 298–301 (1988). https://doi.org/10.1007/BF00174678

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00174678

Key words

Search

Navigation