Work done in the Hoebel laboratory over a decade ago was some of the first to demonstrate a relevant link between ACh in the VTA and feeding related behavior [61]. These findings suggested that an interaction between ACh from pontomesencephalic sources and VTA could also be particularly critical for determining the action of drugs such as cocaine, that increase DA signaling by reuptake blockade. The ability of cocaine to increase extracellular DA is impulse dependent, and the interaction of ACh-mediated excitation of DA neurons, coupled with DA reuptake blockade may effectively increase the impact of cocaine on the mesolimbic system. We have found support for this hypothesis in our finding that repeated exposure to nicotine increased break points for cocaine self-administration on a progressive ratio reinforcement schedule [31].
