BOTH NICOTINIC AND MUSCARINIC RECEPTORS IN VENTRAL TEGMENTAL AREA CONTRIBUTE TO BRAIN-STIMULATION

Cholinergic neurons of the pedunculopontine tegmental nucleus (Ch5) an d laterodorsal tegmental nucleus (Ch6) monosynaptically activate dopam ine neurons of the substantia nigra and ventral tegmental area (VTA) v ia nicotinic and muscarinic receptors. The nicotinic receptors near th e VTA have been proposed to be important for nicotine self-administrat ion in rats and for tobacco smoking in humans. Nicotinic and muscarini c blockers were microinjected into the VTA of rats trained to lever-pr ess for lateral hypothalamic stimulation via an ipsilateral electrode. The competitive nicotinic blocker dihydro-beta-erythroidine (DH beta E; 5-60 mu g) shifted rate-frequency curves to the right by a mean of 6-27% in a dose-related manner; the noncompetitive nicotinic blocker m ecamylamine (10-300 mu g) produced similar shifts of 7-21%. Atropine ( 30 mu g) shifted the curves to the right by a mean of 82% in three of the sites tested with DH beta E. All blockers decreased maximum bar-pr essing rates significantly in some sites when the shifts were large. T herefore, nicotinic receptors in the VTA make small contributions to t he maintained rewarding effect of brain-stimulation reward in rats, bu t muscarinic receptors in the VTA appear to be more important. (C) 199 7 Elsevier Science Inc.