Interaction between noradrenergic and cholinergic systems in the rat brain: Behavioural function in locomotor activity

Abstract

Anticholinergic drugs such as scopolamine and atropine induce a mild locomotor stimulation when given intraperitoneally to rats. This effect is usually ascribed to interaction between dopaminergic and cholinergic transmission in the striatum or nucleus accumbens. However, an interaction of acetylcholine with noradrenergic systems is also apparent from biochemical data and the results reported here indicate that at least part of the locomotor activity induced by scopolamine or atropine involves a noradrenergic component. Depletion of forebrain noradrenaline by injection of 4 μg of the selective neurotoxin 6-hydroxydopamine into the dorsal bundle was found to potentiate the locomotor activation induced by various doses of scopolamine or atropine. This was a central effect since methylscopolamine, which does not pass the blood-brain barrier, failed to induce locomotor activity and was not affected by the noradrenergic lesion. The noradrenergic interaction was restricted to cholinergic drugs since locomotor activity induced by the indirect dopamine agonist amphetamine was not affected by noradrenaline depletion. These studies show that the interaction between noradrenergic and cholinergic transmission, which has previously been indicated by biochemical analysis, influences behaviour and they also cast some light on the functions of the central noradrenergic system itself.