Neurotrophic factors and the signaling pathways they activate play a role in mediating long-term molecular, cellular, and behavioral adaptations associated with drug addiction. Here we mimicked the biological response of phospholipase C-gamma (PLC gamma) induction in the ventral tegmental area (VTA) observed after chronic morphine using viral-mediated gene transfer. Using a behavioral sensitization paradigm, we demonstrate that microinjections of PLC gamma 1 into distinct (rostral vs. caudal) regions of the VTA result in differential locomotor responses to morphine.