Ethanol alters the effect of kappa receptor ligands on dopamine release in the nucleus accumbens

Repeated exposure to ethanol has previously been shown to induce alterations in both midbrain dopamine and dynorphin systems. The aim of this study was to investigate functional changes in the sensitivity of dynorphin/κ-receptor systems following repeated ethanol administration, using dopamine as an indirect marker. The effects of κ-opioid receptor ligands on dopamine release in the rat nucleus accumbens were investigated following repeated ethanol administration (2 g/kg body weight, twice daily for 7 days). The selective κ-receptor agonist U50, 488H reduced dopamine levels in both ethanol- and saline-treated animals, although the decline had a later onset and lasted shorter in the ethanol-treated group. Nor-binaltorphimine, a κ-antagonist, produced a significant increase of dopamine in ethanol-treated rats, but lacked effect in the saline-treated group. This change in responsiveness of dopamine neurons following repeated ethanol administration could be related to changes in the sensitivity of κ-receptor systems and/or an increase in dynorphin tone in the nucleus accumbens.