Adult Plasticity

Stimulant drugs, such as amphetamine, induce locomotor-activating and rewarding effects by increasing striatal extracellular dopamine levels. These behavioral and neurochemical effects become sensitized upon repeated drug administration. Sensitization develops gradually and is long-lasting, suggesting alterations in the organization of dopamine circuitry. Consistent with our findings that netrin-1 receptors are expressed by dopamine neurons in the adult brain, we have shown a role for netrin-1 in drug-induced dopamine plasticity in the adult. Our goal is to establish the precise role that these proteins play on the development and expression of behavioral sensitization. We conduct molecular, neurochemical, neuroanatomical and behavioral experiments in adult rats and transgenic mice. These studies are aimed at determining a) the underlying mechanisms by which drugs and other stressors induce enduring changes in dopamine neurons and their connections and b) how these alternations leave this circuitry more vulnerable to events that subsequently activate it.