Functional presynaptic α6-containing nicotinic acetylcholine receptors participate in nicotine reward in the VTA: where and how

In the ventral tegmental area (VTA), [alpha]6-nAChRs express abundantly, but their location, function, pharmacology, and roles in cholinergic modulation of dopaminergic (DA) neurons remain elusive. Using a VTA neuron-adherent bouton preparation, we report that functional [alpha]6-nAChRs are located on GABAergic presynaptic boutons, where they mediate cholinergic modulation of GABA release onto DA neurons. Smoking-relevant concentrations of nicotine desensitize [alpha]6-nAChRs, cause a disinhibition in DA neurons and consequently mediate nicotine reward.