Presynaptic muscarinic receptors on dopaminergic terminals in the nucleus accumbens

Levels of muscarinic receptors were measured in the nucleus accumbens of rat following 0.8 microgram 6-hydroxydopamine or vehicle injections (0.2 microliter into the ventral tegmental area to investigate whether the dopaminergic terminals destroyed by this procedure bear muscarinic receptors. Dopamine levels in the nucleus accumbens ipsilateral to the injection of 6-hydroxydopamine were substantially reduced by 83% as compared to the unlesioned side after 7 days. Significant decreases in the specific binding of [3H]N-methylscopolamine of 9 and 15% were also seen in the nucleus accumbens ipsilateral to the lesion after 7 and 14 days respectively. The class of muscarinic receptor depleted by the lesion was further investigated using [3H]oxotremorine-M to label the 'super high' affinity binding sites. The percentage occupancy of total muscarinic receptors by [3H]oxotremorine-M was significantly decreased by lesion e.g. 23% after 7 days indicting a selective loss of 'super high' affinity binding sites. The lesion caused no change in the affinity constant for the muscarinic antagonist, propylbenzilylcholine. Studies of the binding of the agonist carbachol and oxotremorine-M by competition with [3H] propylbenzilylcholine showed little change in the concentrations or affinity constants of the 'high' and 'low' affinity binding sites with the 6-hydroxydopamine lesion.