Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 345, Issue 6, pp 627–632

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. Heijna
  • François Hogenboom
  • Arie H. Mulder
  • Anton N. M. Schoffelmeer
Article

DOI: 10.1007/BF00164575

Cite this article as:
Heijna, M.H., Hogenboom, F., Mulder, A.H. et al. Naunyn-Schmiedeberg's Arch Pharmacol (1992) 345: 627. doi:10.1007/BF00164575

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 typesDopamine releaseAcetylcholine releasePotassium channelsAdenylate cyclase

Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • Menno H. Heijna
    • 1
  • François Hogenboom
    • 1
  • Arie H. Mulder
    • 1
  • Anton N. M. Schoffelmeer
    • 1
  1. 1.Department of PharmacologyFree University, Medical FacultyBT AmsterdamThe Netherlands