Our study also supports previous behavioral and microdialysis studies on the role of ACh in the VTA. You et al (2008) demonstrated that ACh release in the VTA of rats was elevated by both cocaine seeking and cocaine taking. The amount of ACh elevation associated with cocaine taking depended on cocaine training experience, as rats that controlled the self-administration of cocaine had an elevation in ACh during a cocaine self-administration trial, greater than that in rats that passively received cocaine and had no prior cocaine training. During cocaine-seeking, when saline was substituted for cocaine, so that animals could respond for cocaine, but received saline, cocaine trained rats showed higher levels of VTA ACh, compared to saline-trained animals in the same environment. Thus, contextual cues, such as insertion of the active lever, which predicted cocaine for cocaine-trained rats, were important factors 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
