Arecoline excites rat locus coeruleus neurons by activating the M2-muscarinic receptor.

The action of arecoline on rat locus coeruleus neurons was studied by intracellular recording from the in vitro brain slice preparation. Superfusion of arecoline (0.1-100 microM) caused two dose-related effects, an increased firing rate and, in neurons previously hyperpolarized to a constant potential by passing a steady hyperpolarizing current across the membrane, depolarization. Both effects were associated with a reduction in membrane input resistance. Moreover, the arecoline-induced excitatory effects were antagonized by the muscarinic receptor antagonist, atropine, but not by the nicotinic receptor antagonist, hexamethonium. Methoctramine, a selective M2-muscarinic receptor antagonist, was also effective in reversing the arecoline-induced effects, with a dissociation equilibrium constant of 14.2+/-1.2 nM (n=6). These results therefore suggest that arecoline exerts its excitatory actions by binding to M2-muscarinic receptors on the cell membrane of neurons of the locus coeruleus.