for the source of ACh associated with cocaine seeking. On the other hand, ACh release that was sustained for hours after cocaine self-administration was attributed to cocaine taking. ACh effects were mediated mostly by muscarinic receptors, as blocking them in the VTA enhanced lever-pressing for cocaine. In our study, however, the M2 agonist OxoSQ applied in the LDTg suppressed lever pressing for cocaine. This discrepancy may be explained by the fact that You et al. (2008) measured lever pressing under an FR-1 schedule as opposed to a PR schedule. In their study, time-outs (see methods: TO) did not include a retraction of the active lever, and thus lever pressing was counted even though increased pressing had no consequence. Our study, however, confirms the findings of You et al. (2008), with regard to the idea that blocking cholinergic input may reduce the salience of contextual cues that predict reward. This view is also congruent with results from the M5 knock out studies (Thomsen et al., 2005), which showed lowered acquisition of cocaine self-administration in null mutant mice.
