Addiction, compulsive drug seeking, and the role of frontostriatal mechanisms in regulating inhibitory control.

School of Psychology and Psychiatry, Monash University, Clayton, Victoria 3800, Australia.
Neuroscience & Biobehavioral Reviews (Impact Factor: 9.44). 03/2010; 35(2):248-75. DOI:10.1016/j.neubiorev.2010.03.001
Source: PubMed

ABSTRACT A principal feature of drug addiction is a reduced ability to regulate control over the desire to procure drugs regardless of the risks involved. Traditional models implicated the neural 'reward' system in providing a neurobiological model of addiction. Newer models however, have expanded on this circuitry to include two separate, but interconnecting systems, the limbic system in the incentive sensitization of drugs, and the prefrontal cortex (PFC) in regulating inhibitory control over drug use. Until the recent developments in neuroimaging and brain stimulation techniques, it has been extremely difficult to assess the involvement of the PFC in addiction. In the current review, we explore the involvement of the frontostriatal circuitry in regulating inhibitory control, and suggest how dysregulation of these circuits could be involved in an increased difficulty in ceasing drug use. Following this, we investigate the recent neuropsychological, neuroimaging and brain stimulation studies that explore the presence of these inhibitory deficits, and frontostriatal dysfunctions, across various different substance groups. Further insight into these deficits could contribute to the development of treatment strategies which target these cognitive impairments, and frontostriatal dysfunction, in reducing drug-seeking behaviors.

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    ABSTRACT: Objectives Despite efforts that have increased smoking regulation, cigarette taxation, and social stigma, cigarette smoking remains the leading cause of preventable death worldwide, and a significant personal and public economic burden. In the U.S., intermittent smokers comprise approximately 20% of all smokers and represent a stable, non-dependent group that may possess protective factors that prevent the transition to dependence. One possibility is that intermittent smokers have intact CNS frontal regulatory and control mechanisms that enable resistance to nicotine-induced changes. Methods The present study measured inhibitory control using a flanker task and a go-nogo continuous performance tasks in daily dependent smokers, intermittent non-dependent smokers, and nonsmokers. Event-related potential (ERP) measures of were concurrently recorded to measure performance monitoring via event-related negativity (ERN) and error positivity (Pe) components during error trials for each task. Results In both tasks, behavioral and ERN measures did not differ between groups; however, amplitude of the Pe component was largest among intermittent smokers. Conclusions Thus, intermittent smokers differed from both daily smokers and nonsmokers on error processing, potentially revealing neuroprotective cognitive processes in nicotine dependence. Significance A better understanding of factors that mediate behavioral regulation may provide novel treatment approaches that help individuals achieve controlled smoking or cessation.
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