The Interaction between GABA-Ergic Drugs and Dopaminergic Stimulants

  • J. Arnt
  • A. V. Christensen
  • J. Scheel-Krüger
Part of the NATO Advanced Study Institutes Series book series (NSSA, volume 16)


In the human brain there is evidence for a functional dysbalance between γ-aminobutyric acid (GABA) and dopamine in Parkinson’s disease and Huntington’s chorea (McGeer and McGeer, 1976). In both diseases there are a pronounced decrease in GABA and its synthesizing enzyme glutamic acid decarboxylase (GAD) in the basal ganglia system. Dopamine is in addition decreased in parkinsonism. A useful new therapeutic strategy for these diseases might be a supplementary treatment with drugs which increase GABA receptor activity. Obviously there is a need for methods measuring the specific pharmacological effects of GABA-ergic drugs in vivo. This lack has consequently limited conclusions based on clinical trials with apparently unspecific drugs like baclofen (Naik et al, 1976). As a model compound we used muscimol which until now has shown to be the most potent and selective GABA-agonist able to penetrate the bloodbrain barrier (Naik et al, 1976; Scheel-Krüger et al, 1977 a). We investigated the behavioural interactions of different putative GABA-ergic drugs with morphine and different dopaminergic stimulants. As an animal model for dopaminergic activity we used the stereotyped behaviour and locomotor activity induced by methylphenidate, apomorphine and cocaine.


Locomotor Activity Glutamic Acid Decarboxylase Dopaminergic Stimulant Locomotor Stimulant Effect Gaba Receptor Agonist 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Haefely, W., Kulcsar, A., Möhler, H., Pieri, L., Pole, P., and Schaffner, R., 1977, Possible involvement of GABA in the central actions of benzodiazepines, in “Mechanism of Action of Benzodiazepines” (E. Costa and P. Greengard, eds.), pp. 131–151, Raven Press, New York.Google Scholar
  2. Krogsgaard-Larsen, P., Johnston, G.A.R., Lodge, D., and Curtis, D. R., 1977, A new class of GABA agonist, Nature 268: 53–55.PubMedCrossRefGoogle Scholar
  3. McGeer, P.L., and McGeer, E.G., 1976, Enzymes associated with the metabolism of catecholamines, acetylcholine and GABA in human controls and patients with Parkinson’s disease and Huntington’s chorea, J. Neurochem 26: 65–76.PubMedGoogle Scholar
  4. Naik, S.R., Guidotti, A. and Costa, E, 1976, Central GABA receptor agonists: Comparison of muscimol and baclofen, Neuropharmacology 15: 479–484.PubMedCrossRefGoogle Scholar
  5. Pedersen, V. and Christensen, A.V., 1972, Antagonism of methylphenidate-induced stereotyped gnawing in mice, Acta Pharmacol Toxicol. 31: 488–496.CrossRefGoogle Scholar
  6. Scheel-Krüger, J., Arnt, J., and Magelund, G., 1977 a, Behavioural stimulation induced “by muscimol and other GABA agonists injected into the substantia nigra, Neuroscience Letters 4: 351–356.Google Scholar
  7. Scheel-Krüger, J., Brasstrup, C., Nielsen, M., Golembiowska, K. and Mogilnicka, E., 1977, Cocaine: Discussion of the role of dopamine in the biochemical mechanism of action, in “Cocaine and other stimulants” (E.H. Ellinwood and M.M. Kilbey, eds.), pp. 373–407, Plenum Press, New York.CrossRefGoogle Scholar
  8. Scheel-Krüger, J., Golembiowska, K., and Mogilnicka, E., 1977, Evidence for increased apomorphine sensitive dopaminergic effects after acute treatment with morphine, Psychopharmacology, 53: 55–63.PubMedCrossRefGoogle Scholar
  9. Scheel-Kruger, J., Cools, A.R., and Honig, W., 1977, Muscimol antagonizes the ergometrine-induced locomotor activity in nucleus accumbens: Evidence for a GABA-dopaminergic interaction, Europ. J. Pharmacol 42: 311–313.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1978

Authors and Affiliations

  • J. Arnt
    • 1
  • A. V. Christensen
    • 2
  • J. Scheel-Krüger
    • 3
  1. 1.Psychopharmacological Research Laboratory Sct.Hans Mental HospitalRoskildeDenmark
  2. 2.Department of PharmacologyRoyal Danish School of PharmacyCopenhagenDenmark
  3. 3.Department of Pharmacology and ToxicologyH. Lundbeck & Co.CopenhagenDenmark

Personalised recommendations