however, the initial peak of ACh in the VTA (which was short in duration) depended upon the history of cocaine self-administration. Passive infusion of cocaine to cocaine-experienced animals produced an initial peak increase in ACh levels in the VTA that was not seen in cocaine naïve animals infused with cocaine for the first time (You et al, 2008). Blocking of muscarinic receptors in the VTA decreased DA levels in the VTA and increased lever pressing for cocaine (You et al, 2008). Thus, muscarinic receptors in the VTA seem to be especially important in cocaine taking, and ACh appears to contribute to the rewarding effects of cocaine. In fact, although the initial peak increase in ACh level was affected by cocaine experience, the more prolonged increase in ACh level was not dependent upon cocaine experience (You et al, 2008). Other studies on nicotinic receptors in the VTA also support the importance of ACh in the escalation of cocaine self-administration. For example, rats trained to self-administer cocaine in short access sessions do not show escalation of cocaine self-administration. However, those trained to self-administer cocaine in extended access sessions do show escalation, and when the nicotinic receptor antagonist mecamylamine was included with cocaine
