There is a substantial amount of evidence supporting the idea that activation of the DAergic system is required for the emergence of the sensitized locomotor response, with induction of sensitization attributed to the VTA and the expression to the NAc (Mao and McGehee, 2010). Through actions on nAChRs in this system, both nicotine and ethanol influence neuronal activity firing rate (Mereu et al., 1987), bursting activity (Zhang and Sulzer, 2004), and corresponding neurotransmitter release—including DA, GABA, and Glutamate, which are surely contributing to the drugs' locomotor-stimulating effects (Nestby et al., 1997; Guo et al., 1998; Tzschentke, 2001; Lambe et al., 2003; Broadbent et al., 2005; Meyer et al., 2008; Mao et al., 2011). For example, intracranial injections of nicotine directly into the VTA results in locomotor sensitization (Reavill and Stolerman, 1990; Kita et al., 1992) and is associated with an increase in DA and c-Fos-like immunoreactivity (an indicator of neuronal activation) in the NAc (Panagis et al., 1996; Shim et al., 2001). For these reasons, behavioral sensitization induced by nicotine and ethanol can be partially attributed to their actions on nAChRs in the midbrain reward pathway.
