Role of primary sensory neurons in the central effects of nicotine

Utilizing single unit recording techniques the nicotine-induced excitation of noradrenaline (NA)-containing neurons in the locus coeruleus (LC) was analyzed. Low doses of nicotine (40-160 micrograms, IV) were found to dose-dependently increase the LC firing rate. The effect was antagonized by pretreatment with the quaternary ganglionic blockers hexamethonium (12 mg/kg, IP) and chlorisondamine (0.3 mg/kg, IV). Also, neonatal treatment with capsaicin, a procedure that is associated with a selective degeneration of primary sensory C-fibre afferents, clearly antagonized the effect of nicotine on LC neurons. The typical effect of nicotine on LC discharge was, in all essentials, mimicked by the quaternary nicotinic agonist tetramethylammonium (TMA). We here propose that the action of nicotine on central NA neurons is primarily executed peripherally via activation of primary sensory C-fibre afferents.