K+-evoked release of met-enkephalin from rat striatum in vitro: effect of putative neurotransmitters and morphine.

The effects of drugs on the K+-evoked release of met-enkephalin from superfused rat striatal slices were investigated using a specific radioimmunoassay. GABA, at concentrations of 50 microM and 100 microM, and the GABA agonist muscimol (50 microM), significantly inhibited the release. The inhibitory effect of GABA was reversed by picrotoxin suggesting that GABA inhibition is mediated by GABA receptors. Selected concentrations of the dopamine agonists apomorphine and ergonovine, as well as of haloperidol, acetylcholine, carbachol, noradrenaline, glutamic acid and substance P, had no effect on the release of metenkephalin. Increases in the evoked release (80%) and striatal enkephalin content (60%) were found in rats after chronic haloperidol administration, pointing to an increase in the synthesis and utilization of striatal enkephalin. No differences were found between the release from slices from morphine-tolerant/dependent and naive rats or after addition of naloxone to slices derived from tolerant/dependent animals. Selected concentrations of morphine and naloxone had no effect on release suggesting the absence of a mechanism for the regulation of enkephalin release involving autoreceptors.