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

Slices of the rabbit hippocampus were preincubated 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 kappa-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 mu-agonist DAGO (D-Ala2-Gly-ol5-enkephalin) showed significant depressant effects, two other mu-agonists morphine and morphiceptine, as well as the delta-agonists DADLE (D-Ala2-D-Leu5-enkephalin) and Leu-enkephalin were much less inhibitory. The preferential mu-antagonist (-)naloxone as well as (-)MR 2266 [(-)N-(3-furylmethyl)-alpha-noretazocine], a preferential kappa-antagonist, did not increase acetylcholine release when given alone, but antagonized the effect of ethylketocyclazocine; (-)MR 2266 (Ke: 1.6 nmol/l) was about 4 times more potent than (-)naloxone (Ke: 6.3 nmol/l). The inhibitory effects of DAGO and DADLE were abolished by (-)MR 2266 (0.1 mumol/l) but not by the delta-antagonist ICI 174864 (N,N-diallyl-Tyr-Aib-Phe-Leu-OH, 0.3 mumol/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 kappa-receptors; in addition, mu-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 mu- rather than kappa-receptors may modulate acetylcholine release.