Kevin S Murnane1, Leonard L Howell. 1. Yerkes National Primate Research Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329, USA.
Abstract
RATIONALE: Neuroimaging techniques have led to significant advances in our understanding of the neurobiology of drug taking and the treatment of drug addiction in humans. Neuroimaging approaches provide a powerful translational approach that can link findings from humans and laboratory animals. OBJECTIVE: This review describes the utility of neuroimaging toward understanding the neurobiological basis of drug taking and documents the close concordance that can be achieved among neuroimaging, neurochemical, and behavioral endpoints. RESULTS: The study of drug interactions with dopamine and serotonin transporters in vivo has identified pharmacological mechanisms of action associated with the abuse liability of stimulants. Neuroimaging has identified the extended limbic system, including the prefrontal cortex and anterior cingulate, as important neuronal circuitry that underlies drug taking. The ability to conduct within-subject longitudinal assessments of brain chemistry and neuronal function has enhanced our efforts to document long-term changes in dopamine D2 receptors, monoamine transporters, and prefrontal metabolism due to chronic drug exposure. Dysregulation of dopamine function and brain metabolic changes in areas involved in reward circuitry have been linked to drug taking behavior, cognitive impairment, and treatment response. CONCLUSIONS: Experimental designs employing neuroimaging should consider well-documented determinants of drug taking, including pharmacokinetic considerations, subject history, and environmental variables. Methodological issues to consider include limited molecular probes, lack of neurochemical specificity in brain activation studies, and the potential influence of anesthetics in animal studies. Nevertheless, these integrative approaches should have important implications for understanding drug taking behavior and the treatment of drug addiction.
RATIONALE: Neuroimaging techniques have led to significant advances in our understanding of the neurobiology of drug taking and the treatment of drug addiction in humans. Neuroimaging approaches provide a powerful translational approach that can link findings from humans and laboratory animals. OBJECTIVE: This review describes the utility of neuroimaging toward understanding the neurobiological basis of drug taking and documents the close concordance that can be achieved among neuroimaging, neurochemical, and behavioral endpoints. RESULTS: The study of drug interactions with dopamine and serotonin transporters in vivo has identified pharmacological mechanisms of action associated with the abuse liability of stimulants. Neuroimaging has identified the extended limbic system, including the prefrontal cortex and anterior cingulate, as important neuronal circuitry that underlies drug taking. The ability to conduct within-subject longitudinal assessments of brain chemistry and neuronal function has enhanced our efforts to document long-term changes in dopamine D2 receptors, monoamine transporters, and prefrontal metabolism due to chronic drug exposure. Dysregulation of dopamine function and brain metabolic changes in areas involved in reward circuitry have been linked to drug taking behavior, cognitive impairment, and treatment response. CONCLUSIONS: Experimental designs employing neuroimaging should consider well-documented determinants of drug taking, including pharmacokinetic considerations, subject history, and environmental variables. Methodological issues to consider include limited molecular probes, lack of neurochemical specificity in brain activation studies, and the potential influence of anesthetics in animal studies. Nevertheless, these integrative approaches should have important implications for understanding drug taking behavior and the treatment of drug addiction.
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