| Abstrakt: |
The release of C-ACh from rat nucleus accumbens slices, induced by 15 mM [K], was inhibited by the µ- and δ-opioid agonists DAMGO and DPDPE, respectively, whereas only the κ agonist U50,488 reduced the release of H-DA. The opioid receptors involved appear to be localized on nerve terminals, since blockade of action potential propagation by 1 μM TTX did not diminish the inhibitory effects of DAMGO, DPDPE or U50,488. Enhancement of the potassium concentration in the superfusion medium to 56 mM with simultaneous reduction of the Ca concentration from 1.2 mM to 0.12 mM induced a release similar to that caused by 15 mM K and 1.2 mM Ca. Under this conditions, the inhibitory effects of both DAMGO and DPDPE on stimulated C-ACh release were reduced, whereas the inhibition of evoked H-DA release caused by U50,488 was not affected. Activation of µ- as well as δ-opioid receptors by DAMGO and DPDPE, respectively, inhibited forskolin-stimulated adenylate cyclase activity. However, increasing the intracellular cAMP levels with 0.3 mM 8-bromo-CAMP affected neither the depolarization-induced release of C-ACh or H-DA from accumbens slices nor the inhibitory effects of opioid receptor activation thereon. The results indicate that the mechanism by which functional µ- and δ receptors presynaptically inhibit the depolarization-induced C-ACh release from nucleus accumbens slices is likely to involve an increase of potassium channel conductance. In contrast, activation of κ-opioid receptors, which inhibits depolarization-evoked H-DA release, apparently does not result in a hyperpolarization of (dopaminergic) nerve terminals. In none of these inhibitory effects presynaptic adenylate cyclase appears to be involved. [ABSTRACT FROM AUTHOR] |
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