Article

Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 345, Issue 6, pp 627-632

First online:

Opioid receptor-mediated inhibition of 3H-dopamine and 14C-acetylcholine release from rat nucleus accumbens slices

A study on the possible involvement of K+ channels and adenylate cyclase
  • Menno H. HeijnaAffiliated withDepartment of Pharmacology, Free University, Medical Faculty
  • , François HogenboomAffiliated withDepartment of Pharmacology, Free University, Medical Faculty
  • , Arie H. MulderAffiliated withDepartment of Pharmacology, Free University, Medical Faculty
  • , Anton N. M. SchoffelmeerAffiliated withDepartment of Pharmacology, Free University, Medical Faculty

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Summary

The release of 14C-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 3H-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 Ca2+ 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 14C-ACh release were reduced, whereas the inhibition of evoked 3H-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 14C-ACh or 3H-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 14C-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 3H-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.

Key words

Opioid receptor types Dopamine release Acetylcholine release Potassium channels Adenylate cyclase