Acetylcholine receptor effects on accumbal shell dopamine-mediated turning behaviour in rats

Abstract

The nature of acetylcholine receptor effects on dopaminergic functions within the nucleus accumbens shell was studied in rats, using turning behaviour as read-out parameter. Unilateral injections of the acetylcholine receptor agonist, carbachol (1.0–5.0 μg), into the nucleus accumbens shell dose-dependently elicited contraversive circling. Unilateral injections of the combination of a fixed dose of the dopamine D 2 receptor agonist, quinpirole (10.0 μg), with increasing doses of the dopamine D 1 receptor agonist, SKF 38393 (1.0–5.0 μg), into the nucleus accumbens shell dose-dependently elicited contraversive pivoting. The same held for the combination of a fixed dose of SKF 38393 (5.0 μg) with increasing doses of quinpirole (5.0 and 10.0 μg), which was injected into the nucleus accumbens shell. The nicotinic acetylcholine receptor antagonist, mecamylamine (5.0 and 10.0 μg), injected into the nucleus accumbens shell, which alone did not elicit any turning behaviour, significantly suppressed both the contraversive circling induced by carbachol (5.0 μg) and the contraversive pivoting induced by the mixture of SKF 38393 (5.0 μg) and quinpirole (10.0 μg). The muscarinic acetylcholine receptor antagonist, methylscopolamine (1.0 and 2.5 μg), injected into the nucleus accumbens shell, which alone did not elicit any turning behaviour, significantly suppressed the contraversive circling induced by carbachol (5.0 μg), whereas it significantly increased the contraversive pivoting induced by both the mixture of SKF 38393 (1.0 μg) and quinpirole (10.0 μg) and the mixture of SKF 38393 (5.0 μg) and quinpirole (5.0 μg). Neither SKF 38393 (5.0 μg) nor quinpirole (10.0 μg) injected into the nucleus accumbens shell affected the contraversive circling induced by carbachol (5.0 μg). Carbachol (1.0 μg) injected into the nucleus accumbens shell caused a slight initial potentiation followed by an inhibition of the contraversive pivoting induced by the mixture of SKF 38393 (5.0 μg) and quinpirole (10.0 μg). These results confirm that stimulation of both nicotinic and muscarinic acetylcholine receptors in the nucleus accumbens shell is required for the accumbens-dependent, acetylcholine-mediated circling. The study provides the original evidence that stimulation of nicotinic acetylcholine receptors in the nucleus accumbens shell is required for the accumbens-dependent, dopamine-mediated pivoting. Finally, the present study shows that muscarinic acetylcholine receptors in the nucleus accumbens shell play an inhibitory role in the production of the accumbens-dependent, dopamine-mediated pivoting.