One important source of cholinergic modulation of VTA DAergic neurons arises from the lateral dorsal tegmental nucleus (LDTg). DA cells that are modulated by the LDTg cholinergic input project to the NAc (Omelchenko and Sesack, 2005; 2006). Another much smaller cholinergic modulation of the VTA comes from the pedunculopontine nucleus (PPTg) (Oakman et al., 1995; Yeomans et al., 1993). Lesions of the LDTg, but not PPTg, attenuate the DA elevation in NAc induced by intra-VTA microinjection of neostigmine (Blaha et al, 1996). Agonists of ACh and glutamate receptors are known to activate VTA DA cells and to elevate DA levels in the NAc (Grenhoff et al, 1986; Blaha et al, 1996; Lester et al, 2008). Self-administration experiments, combined with microdialysis methods, have shown that both active (self-administered) and passive cocaine increase ACh levels in the VTA (You et al, 2008); however, the initial peak of ACh in the VTA (which was short in duration) depended upon the history of cocaine self-administration. Passive infusion of cocaine to cocaine-experienced animals produced an initial peak increase in ACh levels in the VTA that
