Both nicotinic and muscarinic receptors in ventral tegmental area contribute to brain-stimulation reward.

Cholinergic neurons of the pedunculopontine tegmental nucleus (Ch5) and laterodorsal tegmental nucleus (Ch6) monosynaptically activate dopamine neurons of the substantia nigra and ventral tegmental area (VTA) via nicotinic and muscarinic receptors. The nicotinic receptors near the VTA have been proposed to be important for nicotine self-administration in rats and for tobacco smoking in humans. Nicotinic and muscarinic blockers were microinjected into the VTA of rats trained to lever-press for lateral hypothalamic stimulation via an ipsilateral electrode. The competitive nicotinic blocker dihydro-beta-erythroidine (DH beta E; 5-60 micrograms) shifted rate-frequency curves to the right by a mean of 6-27% in a dose-related manner; the noncompetitive nicotinic blocker mecamylamine (10-300 micrograms) produced similar shifts of 7-21%. Atropine (30 micrograms) 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-pressing rates significantly in some sites when the shifts were large. Therefore, nicotinic receptors in the VTA make small contributions to the maintained rewarding effect of brain-stimulation reward in rats, but muscarinic receptors in the VTA appear to be more important.