Our major aim of this project is to determine detailed neural connections involved in drug reinforcement. Behavioral studies indicate that the mesolimbic dopamine system is functionally heterogeneous. The medial portion of the ventral striatum, which includes the medial accumbens shell and medial olfactory tubercle, is more responsible for primary reinforcing effects of psychomotor stimulants than the lateral ventral striatum, which includes the accumbens core, ventral shell, and lateral tubercle. In the dopamine cell-body region, the posterior VTA and the central linear nucleus raphe are more responsible than the anterior VTA for the reinforcing effects of a number of drugs including opiates and cholinergic agents. Based on these behavioral findings, we hypothesize that the reward-trigger zones in the ventral striatum (i.e., the medial accumbens shell and medial olfactory tubercle) receives projections from the reward-trigger zones in the ventral midbrain (i.e., the posterior VTA and central linear nucleus). When the retrograde tracer Fluorogold (FG) was deposited into the medial ventral striatum (the medial shell or medial tubercle), FG-filled cells were found largely in the posteromedial compartment of the VTA and the central linear nucleus. On the other hand, when FG was deposited into the lateral ventral striatum (the core, lateral shell, or lateral tubercle), FG-filled cells were found mostly in the lateral portion of the VTA. Our results suggest that the reward-trigger zones in the medial ventral striatum receive input from the reward-trigger zones in the posteromedial ventral midbrain.
