Nicotine-induced DA release in the NAc has been reported to be mediated by stimulation of nicotinic acetylcholine receptors (nAChRs) on cells of the VTA that project to the NAc rather than by nicotinic receptors within the NAc itself (Nisell et al. 1994). Lesioning of mesolimbic VTA neurons projecting to the NAc leads to decreased nicotine self-administration (Corrigall et al. 1992; Lanca et al. 2000). Additionally, the effects of nicotine on the dopaminergic system appear to be modulated by glutamatergic and GABAergic neurons (Picciotto and Corrigall 2002), with nicotine stimulation of gluatamatergic tracts from the prefrontal cortex to the VTA leading to increased DA neuron firing (Kenny and Markou 2001) and GABA agonism leading to a dampening of DA neuron responses (Cousins et al. 2002). Recent work indicates that nicotine administration causes prolonged depression of GABAergic firing, leading to relatively large excitatory (glutamatergic) input into the mesolimbic DA system and increased DA neuron firing (Mansvelder et al. 2002).
