In vivo modulations by GABA-related drugs of met-enkephalin release in basal ganglia of the cat brain.
The influence of the intrapallidal application of GABA-related compounds on the release of Met-enkephalin in the globus pallidus and the caudate nucleus in the two hemispheres was investigated in vivo in the cat. For this purpose, the 4 structures were continuously superfused with an artificial CSF through implanted push-pull cannulae and Met-enkephalin released in superfusates was determined using a specific radioimmunoassay. GABA (10-500 microM) reduced the local release of Met-enkephalin during its application but once the amino acid was removed from the superfusing fluid, an increase in the peptide release was observed. Diazepam (10 microM) induced only an inhibitory effect whereas muscimol (1 microM) stimulated Met-enkephalin release. Opposite changes in Met-enkephalin release were also seen with the GABA antagonists, bicuculline methiodide (1 microM) and picrotoxin (10 microM), suggesting that the local regulation of Met-enkephalin release by GABA related compounds may be mediated by at least two types of GABA receptors. In several cases, the unilateral pallidal application of GABA agonists and antagonists induced significant changes in Met-enkephalin release at distant structures. The most striking effect was observed with diazepam which markedly reduced the peptide release in both caudate nuclei and pallida. These data suggest that GABAergic systems can contribute to some bilateral regulation of striato-pallidal enkephalinergic neurones.
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002415:Cats; D002421:Caudate Nucleus / Q000378:metabolism*; D003975:Diazepam / Q000494:pharmacology; D004347:Drug Interactions; D004744:Enkephalin, Methionine / Q000378:metabolism*; D005260:Female; D005917:Globus Pallidus / Q000378:metabolism*; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology* / Q000502:physiology
D001640:Bicuculline; D003975:Diazepam; D004744:Enkephalin, Methionine; D009118:Muscimol; D010852:Picrotoxin; D005680:gamma-Aminobutyric Acid