μ-opioid receptor-mediated inhibition of the release of radiolabelled noradrenaline and acetylcholine from rat amygdala slices

Abstract

Abstract Presynaptic modulation by opioids of electrically-evoked neurotransmitter release from superfused rat amygdala slices prelabelled with [ 3 H]noradrenaline (NA) and [ 14 C]choline was examined. Both [ 3 H]NA and [ 14 C]acetylcholine release were strongly inhibited by morphine, the mixed δ / μ -receptor agonist [ d -Ala 2 , d -Leu 5 ]enkephalin (DADLE) and the highly selective μ-agonist [ d -Ala 2 , MePhe 4 , Gly-ol 5 ]enkephalin (DAMGO), whereas the highly selective δ-agonist [ d -Pen 2 , d -Pen 5 ]enkephalin and the κ-agonist bremazocine were without effect. The inhibitory effects were potently antagonized by naloxone but not by the selective δ-receptor antagonist fentanylisothiocyanate. When the selective uptake inhibitor desipramine was used to prevent uptake of [ 3 H]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 κ-receptors, whereas transmitter release from noradrenergic and cholinergic nerve fibers is subjected to inhibition by opioids via activation of μ-receptors only. Regional differences and similarities of modulation of neurotransmitter release by opioids in the rat brain are briefly discussed.