Learning to be a cocaine addict: behavioral, pharmacological, and molecular characterization of individual differences in initial learning of cocaine-environment associations

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Title: Learning to be a cocaine addict: behavioral, pharmacological, and molecular characterization of individual differences in initial learning of cocaine-environment associations
Author: Adriane M dela Cruz
Abstract: Cocaine addiction is a chronic , relapsing disease affecting millions of Americans , and differences between individuals modulate the progression from cocaine use to addiction . Learned associations between cocaine and environmental stimuli develop in the subset of patients who become addicted , and exposure to these stimuli facilitates relapse to cocaine -taking . Classical conditioning underlies the development and expression of these learned associations , and several systems implicated in both the behavioral response to cocaine and in learning and memory—e .g . , serotonin2 receptors (5 -HT2R ) , ionotropic & #945 ; -amino -3 -hydroxy -5 -methyl -4 -isoxazole propionic acid (AMPA ) glutamate receptor subunit 1 (GluR1 ) , and a signaling system associated with these receptors (i .e . , the mitogen -activated protein kinase extracellular -signal regulated kinase ; ERK ) in the cortical -limbic regions - -may modulate the acquisition and expression of cocaine -environment associations . Individual differences play a major role in the development of addiction , and behavioral models are needed study these implications in the learning of cocaine -environment associations . We utilized the conditioned place preference (CPP ) paradigm in laboratory rats to model cocaine -environment associations and developed a new method for the analysis of CPP data that allows for identification of factors that modulate individual sensitivity to the development of cocaine -environment associations , pharmacological treatments that are effective only in subpopulations of subjects , and molecular neuroadaptations that differ among subjects susceptible to the development of cocaine -environment associations and non -susceptible individuals . We uncovered roles for 5 -HT2R in the acquisition and expression of cocaine -environment associations formed after a single pairing of cocaine and environment , suggesting a role for these receptors in modulating the development and retrieval of initial cocaine -environment associations . We observed an increase in the phosphorylation of GluR1 and enhanced expression of total ERK protein in the prefrontal cortex upon retrieval of cocaine -environment associations . These studies suggest that the ability to learn strong cocaine -environment associations is associated with a unique set of neuroadaptations and is a predictor of those who will initiate development of a cocaine addiction .
URI: http : / /hdl .handle .net /2152 .3 /233
Date: 2009-09-14

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Learning to be a cocaine addict: behavioral, pharmacological, and molecular characterization of individual differences in initial learning of cocaine-environment associations. Doctoral dissertation, The University of Texas Medical Branch. Available electronically from http : / /hdl .handle .net /2152 .3 /233 .

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