is also supported by recent work on cocaine priming-induced reinstatement of cocaine seeking (Schmidt et al., 2009). Microinjection of an ionotropic glutamate receptor antagonist into the LDTg/PPTg or VTA prior to cocaine priming suppressed lever pressing during cocaine seeking reinstatement trials in rats. This suppression of lever pressing was suggested to reflect reduced glutamatergic activity in a multisynaptic circuit involving glutamatergic input from the medial prefrontal cortex to the LDTg/PPTg, and glutamatergic and cholinergic input from the LDTg/PPTg to the VTA. Similar behavioral results were observed with intra-VTA microinjections of scopolamine, an ACh receptor antagonist. The DA cells of the VTA are innervated by the excitatory cholinergic input from the LDTg (Omelchenko and Sesack, 2006). DA cells in the VTA depolarize in response to muscarine (Lacey et al, 1990) and nicotine (Calabresi et al., 1989), resulting in an increase in DA levels in the NAc (Miller and Blaha, 2005). Muscarinic agonists, such as carbachol in the VTA, are thought to be rewarding since animals learn to lever press for carbachol infusions into the VTA (Ikemoto and Wise, 2002). Conversely, DA levels in the NAc decrease in response to the muscarinic antagonist, scopolamine, and the nicotinic antagonist, mecamylamine, when applied to
