Cocaine Impact on Plasticity & Dendrite Morphology: Interaction with Environmental Complexity One of the most compelling examples of experience-dependent behavioral plasticity, wherebyexperience at one period in life changes behavior for a lifetime, is addiction. The propensity of addicts torelapse, even months to many years after the discontinuation of drug use,and long after withdrawalsymptoms have subsided, provides stark evidence that drug use has long lasting consequences for behaviorand psychological function. Similarly, very long-lasting changes in brain and behavior have been found inanimal models, for example, following sensitization. Persistent experience-dependent changes in behaviorand synaptic organization are presumably due to the effects of drugs and other experiences acting viacoordinated actions on a variety of plasticity-related genes, and perhaps by influencing neurogenesis.Indeed, there is now considerable evidence that drugs of abuse usurp many of the same cellular andmolecular mechanisms responsible for experience-dependent plasticity. This raises the hypothesis thatchanges in synaptic organization produced by experience may interact with those produced by exposure todrugs of abuse. The overall aim of this project is to explore the interaction between the effects of exposure to a drugof abuse, cocaine, and the effects of another life experience (living in a relatively complex environment), onthe expression of key plasticity-related genes and on adult neurogenesis, in two genetically-distinctpopulations of rats that vary in their susceptibility to cocaine. Studies to date support the hypothesis thatexposure to psychostimulant drugs may,under some circumstances and in some brain regions, saturate thepotential for future plasticity (or produce 'metaplasticity') and thus occlude the ability of subsequentexperiences to induce molecules necessary for synaptic reorganization. The hypothesis that exposure topsychostimulant drugs may limit the potential for future plasticity in response to changes in environmentalcondition has important clinical implications. If true, it would suggest that the repeated use of some drugs ofabuse might limit the ability to adapt positively to changes in environmental circumstances. Thus, some ofthe neuropsychological deficits seen in addicts could be due to limits on synaptic plasticity imposed by pastdruguse.
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