The Interaction between GABA-Ergic Drugs and Dopaminergic Stimulants
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.
KeywordsLocomotor Activity Glutamic Acid Decarboxylase Dopaminergic Stimulant Locomotor Stimulant Effect Gaba Receptor Agonist
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