The dopaminergic projection to the nucleus accumbens and prefrontal cortex has been implicated in the mechanisms leading to drug abuse. Upon repeated administration of psychostimulants (i.e., cocaine, d-amphetamine, methamphetamine), animals typically exhibit increased behavioral activation when given a challenge stimulant dose; this phenomenon has been termed """"""""behavioral sensitization"""""""" and it has been related to the increased responses addicted subjects exhibit upon repeated drug intake, particularly to the craving for drug upon withdrawal. Our plan is to explore the brain regions involved in the establishment and expression of such sensitization using electrophysiological techniques. The current views on the mechanisms evoking and expressing sensitization have been built upon several separate studies. The expression of behavioral sensitization, for example, involves the activation of dopamine projections to the nucleus accumbens. On the other hand, the glutamatergic projection from the prefrontal cortex to the ventral tegmental area (the group of cells from which the dopamine projection to the accumbens originates) is required to elicit sensitization. We have been studying the interactions among the prefrontal cortex, nucleus accumbens and ventral tegmental area from a physiological perspective. These regions exhibit mutual interactions that control their information processing; therefore, we hypothesize that such interactions would be altered in sensitized animals. Recording the electrical activity of these neurons simultaneously is an optimal means to address the role of such interactions in the induction and/or expression of behavioral sensitization. In vivo intracellular recordings will be employed to assess changes upon repeated administration of methamphetamine. Methamphetamine was chosen as the sensitizing agent given its recent growth as an abused substance in the U.S.
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