Acetylcholine release in rat nucleus accumbens is regulated through dopamine D₂-receptors

Summary

Experiments in slices of rat nucleus accumbens were carried out in order to investigate whether the release of acetylcholine in this tissue is modulated through dopamine receptors. The slices were preincubated with ³H-choline and then superfused and stimulated electrically twice for 2 min each at a frequency of 3 Hz.

The electrically evoked overflow of tritium averaged 2.9–3.9% of the tritium content of the tissue in the various groups. The D₂-selective agonist quinpirole (0.01–1 μmol/l) reduced the evoked overflow of tritium by maximally 56%, an effect antagonized by the D₂-selective antagonist (−)-sulpiride (1 μmol/l). The D₁-selective agonist 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine (SKF 38393) caused a slight decrease only at the high concentration of 10 μmol/l. (−)-Sulpiride (0.1–10 μmol/l) moderately increased the evoked overflow of tritium when given alone. The dopamine uptake inhibitor nomifensine (10 μmol/l) caused a decrease, and in its presence the increase produced by (−)-sulpiride became much more marked, amounting to maximally 149%. (+)-Sulpiride (0.1–1 μmol/l) failed to change the evoked overflow of tritium in the presence of nomifensine. The dopamine-releasing agent (±)-amphetamine (1 μmol/l) also reduced the evoked overflow, an effect abolished by (−)-sulpiride. Finally, bretylium (1 mmol/l), which blocks the release of dopamine, increased the evoked overflow. (−)-Sulpiride (1 μmol/l) lost its facilitatory effect in slices treated with bretylium.

We conclude that the release of acetylcholine in rat nucleus accumbens, like its release in the nucleus caudatusputamen, is modulated through dopamine D₂-receptors. The receptors are activated by endogenous dopamine under the conditions of these experiments.