MU-OPIOID RECEPTOR-MEDIATED INHIBITION OF THE RELEASE OF RADIOLABELED NORADRENALINE AND ACETYLCHOLINE FROM RAT AMYGDALA SLICES

Presynaptic modulation by opioids of electrically-evoked neurotransmitter release from super-fused rat amygdala slices prelabelled with [H-3]noradrenaline (NA) and [C-14]choline was examined. Both [H-3]NA and [C-14]acetylcholine release were strongly inhibited by morphine, the mixed delta/mu-receptor agonist [D-Ala2, D-Leu5]enkephalin (DADLE) and the highly selective mu-agonist [D-Ala2, MePhe4, Gly-ol5]enkephalin (DAMGO), whereas the highly selective delta-agonist [D-Pen2, D-Pen5]enkephalin and the kappa-agonist bremazocine were without effect. The inhibitory effects were potently antagonized by naloxone but not by the selective delta-receptor antagonist fentanylisothiocyanate. When the selective uptake inhibitor desipramine was used to prevent uptake of [H-3]NA into noradrenergic nerve terminals, but sparing the uptake into dopaminergic nerve terminals, the electrically evoked release of tritium was strongly inhibited by bremazocine but not by DADLE or DAMGO. The data indicate, that in the amygdala transmitter release from dopaminergic nerve fibres is inhibited only via activation of kappa-receptors, whereas transmitter release from noradrenergic and cholinergic nerve fibers is subjected to inhibition by opioids via activation of mu-receptors only. Regional differences and similarities of modulation of neurotransmitter release by opioids in the rat brain are briefly discussed.