DA released in the NAc from the ventral tegmental area (VTA), is critical for the rewarding effects of cocaine (for review see Spanagel and Weiss, 1999). Cocaine, similar to intracranial self-stimulation (ICSS) of the VTA, induces behavioral seeking responses in rats (Wise, 1996). Lesions of the DA terminals in the NAc compromise the self-administration of cocaine (Roberts et al, 1977). Manipulations of VTA DA neurons with pharmacological agents that interact with multiple neurotransmitter systems significantly affect cocaine-induced DA levels in the NAc and cocaine seeking behaviors (for review see Bardo, 1998). Increased acetylcholine (ACh) levels in the VTA in response to cocaine (You et al., 2008) affect both NAc DA levels and reward seeking behaviors, and these effects appear to involve both muscarinic (Forster et al., 2002; Lester et al., 2010) and nicotinic receptors (Clarke and Pert, 1985).
