Evidence for a gamma-aminobutyric acid (GABA) mediation in the benzodiazepine inhibition of the release of Met5-enkephalin elicited by depolarization
Harsing, L.G.; Yang, H.Y.; Costa, E.
Journal of Pharmacology and Experimental Therapeutics 220(3): 616-620
1982
ISSN/ISBN: 0022-3565 PMID: 7038094 Document Number: 190355
The Met5-enkephlalin (ME) content of perfused rat striatal slices decreased by 54% after 66 min of perfusion. The addition to the superfusion fluid of an inhibitor of ME metabolism (Phe-Ala, 0.1 mM) reduced the decrease of the ME content of striatal slices during the superfusion. At the beginning of the superfusion the ME efflux was rapid, it became progressively slower and leveled off to 20 fmol and was antagonized by picrotoxin (5 .mu.M) which impairs the function of GABA receptors. When the slices were prepared from striatum of rats receiving doses of isoniazid, which reduced GABA content by .apprx. 60%, diazepam but not muscimol failed to reduce the efflux of ME elicited by depolarization. Evidently, the inhibition of ME efflux during depolarization elicited by diazepam requires a certain amount of GABA and the availability of GABA receptors, the similar action of muscimol requires only the availability of GABA receptors.