A circuitry model of the expression of behavioral sensitization to amphetamine-like psychostimulants

Repeated exposure to psychostimulants such as cocaine and amphetamine produces behavioral sensitization, which is characterized by an augmented locomotor response to a subsequent psychostimulant challenge injection. Experimentation focused on the neural underpinnings of behavioral sensitization has progressed from a singular focus on dopamine transmission in the nucleus accumbens and striatum to the study of cellular and molecular mechanisms that occur throughout the neural circuitry in which the mesocorticolimbic dopamine projections are embedded. This research effort has yielded a conglomerate of data that has resisted simple interpretations, primarily because no single neuronal effect is likely to be responsible for the expression of behavioral sensitization. The present review examines the literature and critically evaluates the extent to which the neural consequences of repeated psychostimulant administration are associated with the expression of behavioral sensitization. The neural alterations found to contribute to the long-term expression of behavioral sensitization are centered in a collection of interconnected limbic nuclei, which are termed the 'motive' circuit. This neural circuit is used as a template to organize the relevant biochemical and molecular findings into a model of the expression of behavioral sensitization.