Possible behavioural function for noradrenaline–acetylcholine interaction in brain

Abstract

IN the peripheral nervous system, acetylcholine (ACh) acts on presynaptic muscarinic receptors to inhibit the release of noradrenaline (NA) from nerve terminals and by way of nicotinic presynaptic receptors to stimulate release¹. A NA–ACh interaction has also been postulated^2–7 to occur in the central nervous system (CNS). Cholinergic agonists decrease the levels of NA in various brain areas^5,6, affect the release of NA in in vitro preparations^3,4 and have similar effects in vivo as measured by increased metabolites of NA (ref. 2). A reciprocal interaction, that of NA modulating ACh release in the CNS does not seem to occur, according to evidence⁸ available at present. We report here that depletion of forebrain NA by intracerebral injection of the selective neurotoxin 6-hydroxydopamine (6-OHDA) almost completely blocks the catalepsy induced by cholinergic agonists such as pilocarpine and arecoline^9–12 and enhances the locomotor stimulation caused by the anticholinergic drugs scopolamine and atropine^13–15. Although these actions have most usually been ascribed to an interaction with dopamine (DA) systems^16,17, our data show that functionally significant interactions between ACh and NA systems also occur.