electrical stimulations in the LDTg, they failed to do so when scopolamine was also injected into the VTA. In fact, even when DA efflux reached its peak it plummeted to baseline levels if scopolamine was injected into the VTA. Behavioral studies on M5R -/- mice show that M5 receptors are important in cocaine self-administration and conditioned place preference (Fink-Jensen et al., 2003; Thomsen et al, 2005). Cocaine self-administration on an FR-1 schedule was significantly lower in M5R -/-, compared to wild type M5R +/+, mice (Fink-Jensen et al., 2003). Furthermore, in conditioned place preference tests, M5R -/- mice spent less time in contact with a cocaine-paired floor than did wild type mice, suggesting reduced sensitivity to cocaine conditioned reward. Similarly, motivation of M5R -/- mice for self-administering low to medium doses of cocaine, as expressed by BPs on a PR schedule, was significantly lower than in M5R +/- and M5R +/+ mice (Thomsen et al., 2005). Furthermore, M5R -/- and M5R +/- mice were significantly more inefficient than wild type mice in acquiring self-administration behavior, when low doses of cocaine were used. Our study complements this previous work by suggesting a significant role for cholinergic input to VTA dopaminergic neurons
