Presynaptic opioid receptors modulating acetylcholine release in the hippocampus of the rabbit

Abstract

Slices of the rabbit hippocampus were pre-incubated with ³H-choline, rinsed and superfused continuously. The release of ³H-acetylcholine in these slices, evoked by electrical field stimulation, was strongly reduced by the preferential κ-agonists ethylketocyclazocine, dynorphin A (1–13) and dynorphin A (1–17). Dynorphin A (1–9) and (−)MR 2034 [(−)5,9-dimethyl-2′-OH-2-tetrahydrofurfuryl-6,7-benzomorphan] were less potent, the (+)enantiomer of (−)MR 2034 was ineffective. Whereas the μ-agonist DAGO (d-Ala₂-Gly-ol₅-enkephalin) showed significant depressant effects, two other μ-agonists morphine and morphiceptine, as well as the δ-agonists DADLE (d-Ala₂-d-Leu₅-enkephalin) and Leu-enkephalin were much less inhibitory. The preferential μ-antagonist (−)naloxone as well as (−)MR 2266 [(−)N-(3-furylmethyl)-α-noretazocine], a preferential κ-antagonist, did not increase acetylcholine release when given alone, but antagonized the effect of ethyl-ketocyclazocine; (−)MR 2266 (K _e: 1.6 nmol/l) was about 4 times more potent than (−)naloxone (K _e: 6.3 nmol/l). The inhibitory effects of DAGO and DADLE were abolished by (−)MR 2266 (0.1 μmol/l) but not by the δ-antagonist ICI 174864, (N,N-diallyl-Tyr-Aib-Phe-Leu-OH, 0.3 μmol/l). It is concluded that the release of acetylcholine in the hippocampus of the rabbit is inhibited at the level of the axon terminals via κ-receptors; in addition, μ-receptors may be present. An inhibitory tone of endogenous opioid peptides on hippocampal acetylcholine release could not be demonstrated. Experiments on rat hippocampal slices showed that in this species μ- rather than κ-receptors may modulate acetylcholine release.