Impaired functioning of the mesocorticolimbic dopamine system is associated with psychopathologies such as schizophrenia and drug addiction. Our goal is to understand how changes in dopamine neuron activity may contribute to drug addiction liability. Addiction liability is modeled in rodents, using different behavioral paradigms such as voluntary drug-intake (intravenous self-administration) and drug-seeking tests. Dopamine neuron activity is studied with electrophysiological techniques such as in vivo extracellular and in vitro patch clamp recordings. Using in vivo extracellular recordings, we have shown that different animal models of enhanced addiction liability (spontaneously-present, induced by exposure to stress, or by exposure to addictive drugs) are associated with enhanced impulse activity of midbrain dopamine cells.

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The mechanisms underlying heightened dopamine cell activity that are associated with addiction are unknown. We are using two complementary electrophysiological approaches (in vivo extracellular and in vitro patch clamp recordings) to determine the possible synaptic or intrinsic mechanisms that are responsible for addiction-associated increased cell excitability.We are also in the process of establishing if and why adolescence is a time period of enhanced addiction liability. In this project, adolescent and adult rats will be compared both before and after repeated cocaine exposure to appraise whether individuals exhibit inherent differences, and/or show differential cocaine-induced neuroadaptations that could facilitate self-administration behavior.