Depression of potassium-evoked striatal acetylcholine release by δ-receptor activation: inhibition by cholinoactive agents

Abstract

To examine the role of δ-opioid receptors in the modulation of striatal acetylcholine (ACh) release, the action of D-Pen²,L-Pen⁵-enkephalin, a selective δ-opioid receptor agonist, was tested on [³H]ACh release from slices of the rat caudate–putamen. Slices, incubated with [³H]choline, were superfused with a physiological buffer and stimulated twice by exposure to a high potassium (K⁺) concentration. In the absence of a cholinesterase inhibitor, 1 μM D-Pen²,L-Pen⁵-enkephalin produced a 46 and 35% decrease in the release of [³H]ACh evoked by 15 and 25 mM K⁺, respectively. The depressant action of the enkephalin analogue was concentration dependent, with a maximal effect on K⁺-evoked [³H]ACh release occurring at 1.0 μM, and was completely blocked in the presence of the δ-opioid receptor selective antagonist, ICI 174864 (1 μM). In the presence of the cholinesterase inhibitors physostigmine (10 μM) and neostigmine (10 μM), or the muscarinic receptor agonist oxotremorine (10 μM), D-Pen²,L-Pen⁵-enkephalin did not depress the K⁺-evoked release of [³H]ACh. Atropine (1 μM) blocked the inhibitory effect of physostigmine on the depressant action of D-Pen²,L-Pen⁵-enkephalin. The results of this study indicate that δ-opioid receptor activation is associated with an inhibition of striatal ACh release, but this opioid–cholinergic interaction is not apparent under conditions of presynaptic muscarinic receptor activation.