M2 autoreceptors are important in the regulation of the activity of cholinergic neurons, including those in the LDTg (Calabresi et al., 2000, 1998; Forster and Blaha, 2000; Leonard and Llinas, 1994). Activation of M2 receptors on cell bodies and dendrites of striatal cholinergic interneurons cause inhibitory post-synaptic potentials (IPSPs) via increases in K+ currents combined with decreases in Ca2+ channel conductance (Calabresi et al., 2000, 1998; Yan and Surmeier, 1996). Evidence that M2 receptor activation is associated with induction of IPSPs is also provided by in vivo and in vitro studies in single gene mutant (M2R -/-) mice (for review see Wess et al, 2007). Importantly, blocking M2 receptors in the LDTg with scopolamine or the more selective antagonist, methoctramine, abolishes suppression of cholinergic neurons and thus suppression of DA currents in the NAc (Forster and Blaha, 2000). The possibility that OxoSQ affects M2/4 receptors on non-cholinergic neurons cannot be excluded. Previous work shows that locus coeruleus (LC) noradrenergic neurons interconnect heavily with LDTg neurons (Jones, 1991; Leonard et al., 1995). Interestingly, M2 receptors are present on postsynaptic noradrenergic neurons,
