A great deal of research has focused on the effects of cholinergic agents on the mesolimbic DA system and its short- and long-term modulation (for reviews see (Fagen et al., 2003; Mansvelder et al., 2003), particularly because the addictive effects of nicotine are mediated primarily through stimulation of nAChRs in the VTA (Drenan et al., 2008; Maskos et al., 2005; McGranahan et al., 2011; Picciotto et al., 1998). Cholinergic input from the PPTg and LDTg acting through both mAChRs and nAChRs is critical for modulating the function of the VTA. Stimulation of nAChR and M5-type mAChRs increases the tonic excitability of these DA neurons (Corrigall et al., 2002; Miller and Blaha, 2005; Yeomans and Baptista, 1997). ACh released in the VTA is likely to potentiate glutamatergic synaptic transmission onto DA neurons through α7 nAChRs, and may therefore increase the likelihood of burst firing of these neurons (Grenhoff et al., 1986; Maskos, 2008; McGehee et al., 1995).
