Pharmacological analysis of a cholinergic receptor mediated regulation of brain norepinephrine neurons

Abstract

The significance of the cholinergic receptors within the noradrenergic nucleus locus coeruleus (LC) was analyzed by using single unit recording techniques and microiontophoretic drug application of various cholinergic and anticholinergic drugs. Physostigmine (25--50 micrograms/kg), intravenously administered, caused increased firing of LC neurons and this effect was blocked by scopolamine but not by methylscopolamine. Also nicotine (10--50 micrograms/kg i.v.) caused activation of LC neurons, an effect which was antagonized by the presumed nicotinic antagonist mecamylamine (8 mg/kg) as well as scopolamine (0.5 mg/kg i.v.). The cholinergic receptor within the LC showed specific muscarinic characteristics since microiontophoretic application of various muscarinic agonists caused excitation of LC units, whereas microiontophoretically applied nicotine had no effect. In addition, the acetylcholine (ACh)-induced excitation of the LC neurons was not blocked by nicotinic antagonists but was totally antagonized by the muscarinic agonist scopolamine. Scopolamine, when microiontophoretically applied onto the LC neurons, antagonized the stimulatory effect of systemically injected physostigmine but not that of nicotine. These results suggest that the stimulation of noradrenaline (NA) neurons in the LC by cholinergic drugs such as physostigmine is mediated via cholinergic, muscarinic receptors within this nucleus. The LC activation by nicotine is, however, an indirect effect, probably involving central ACh release and mediated via a non-cholinergic LC input.