Effect of nicotine on single cell activity in the noradrenergic nucleus locus coeruleus.

The effect of nicotine and various cholinergic and anticholinergic drugs on brain noradrenaline (NA) containing neurons in the locus coeruleus (LC) of the rat was studied utilizing single cell recording techniques and microiontophoretic drug application. Nicotine (10--50 micrograms/kg i.v.) caused a dose-dependent, short-lasting increase in the firing rate of NA neurons in the LC. When microiontophoretically applied nicotine had no effect on LC neurons, which in contrast were activated by acetylcholine (ACh) and the muscarinic agonist, bethanechol. The stimulation of NA neurons in the LC by i.v. physostigmine was antagonized by scopolamine but not by methylscopolamine. Also microiontophoretically applied scopolamine specifically antagonized the NA-cell activation by ACh. Consequently, nicotine probably causes an indirect activation of NA neurons in the LC. These cells seem to be equipped with excitatory, cholinergic receptors of muscarinic but not nicotinic character. The LC activating effect of nicotine may be important for its arousal producing properties.