Psychostimulant-Induced Gene Regulation in Corticostriatal Circuits

Handbook of Behavioral Neuroscience 12/2010; 20:501-525. DOI: 10.1016/B978-0-12-374767-9.00029-9


This chapter demonstrates that psychostimulants alter the expression of perhaps hundreds of genes in the cortex and the basal ganglia. These include effector genes such as those encoding neuropeptide transmitters that modulate basal ganglia circuit activity in several nuclei, but also transcription factors that regulate the expression of other genes, as well as a variety of other neuroplasticity-related molecules. The findings of numerous studies show that, in the striatum, psychostimulants affect gene regulation predominantly in neurons that give rise to the direct striatal output pathway, with lesser to minimal molecular effects in the indirect pathway. The chapter reviews that the relative impact on these two pathways is to some degree dependent on cortex-activating contextual variables. For the last two decades, much effort in addiction research has been devoted to understanding the significance of molecular changes in motivation-related striatal domains. However, molecular imaging studies demonstrate that psychostimulant-induced gene regulation is considerably more pronounced in associational and, especially, sensorimotor corticostriatal domains. It concludes that Future work will have to determine the functional consequences of such changes in these latter domains. However, studies indicate that these molecular changes occur in striatal areas associated with switching functions, procedural learning and compulsion. They may thus underlie aberrant habit formation and compulsive behavior that signify drug addiction.

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