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      Sex Differences in Behavioral Dyscontrol: Role in Drug Addiction and Novel Treatments

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          Abstract

          The purpose of this review is to discuss recent findings related to sex differences in behavioral dyscontrol that lead to drug addiction, and clinical implications for humans are discussed. This review includes research conducted in animals and humans that reveals fundamental aspects of behavioral dyscontrol. The importance of sex differences in aspects of behavioral dyscontrol, such as impulsivity and compulsivity, is discussed as major determinants of drug addiction. Behavioral dyscontrol during adolescence is also an important consideration, as this is the time of onset for drug addiction. These vulnerability factors additively increase drug-abuse vulnerability, and they are integral aspects of addiction that covary and interact with sex differences. Sex differences in treatments for drug addiction are also reviewed in terms of their ability to modify the behavioral dyscontrol that underlies addictive behavior. Customized treatments to reduce behavioral dyscontrol are discussed, such as (1) using natural consequences such as non-drug rewards (e.g., exercise) to maintain abstinence, or using punishment as a consequence for drug use, (2) targeting factors that underlie behavioral dyscontrol, such as impulsivity or anxiety, by repurposing medications to relieve these underlying conditions, and (3) combining two or more novel behavioral or pharmacological treatments to produce additive reductions in drug seeking. Recent published work has indicated that factors contributing to behavioral dyscontrol are an important target for advancing our knowledge on the etiology of drug abuse, intervening with the drug addiction process and developing novel treatments.

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          Most cited references234

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          Nucleus accumbens D2/3 receptors predict trait impulsivity and cocaine reinforcement.

          Stimulant addiction is often linked to excessive risk taking, sensation seeking, and impulsivity, but in ways that are poorly understood. We report here that a form of impulsivity in rats predicts high rates of intravenous cocaine self-administration and is associated with changes in dopamine (DA) function before drug exposure. Using positron emission tomography, we demonstrated that D2/3 receptor availability is significantly reduced in the nucleus accumbens of impulsive rats that were never exposed to cocaine and that such effects are independent of DA release. These data demonstrate that trait impulsivity predicts cocaine reinforcement and that D2 receptor dysfunction in abstinent cocaine addicts may, in part, be determined by premorbid influences.
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            High impulsivity predicts the switch to compulsive cocaine-taking.

            Both impulsivity and novelty-seeking have been suggested to be behavioral markers of the propensity to take addictive drugs. However, their relevance for the vulnerability to compulsively seek and take drugs, which is a hallmark feature of addiction, is unknown. We report here that, whereas high reactivity to novelty predicts the propensity to initiate cocaine self-administration, high impulsivity predicts the development of addiction-like behavior in rats, including persistent or compulsive drug-taking in the face of aversive outcomes. This study shows experimental evidence that a shift from impulsivity to compulsivity occurs during the development of addictive behavior, which provides insights into the genesis and neural mechanisms of drug addiction.
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              Delayed reward discounting and addictive behavior: a meta-analysis.

              Delayed reward discounting (DRD) is a behavioral economic index of impulsivity and numerous studies have examined DRD in relation to addictive behavior. To synthesize the findings across the literature, the current review is a meta-analysis of studies comparing DRD between criterion groups exhibiting addictive behavior and control groups. The meta-analysis sought to characterize the overall patterns of findings, systematic variability by sample and study type, and possible small study (publication) bias. Literature reviews identified 310 candidate articles from which 46 studies reporting 64 comparisons were identified (total N=56,013). From the total comparisons identified, a small magnitude effect was evident (d= .15; p< .00001) with very high heterogeneity of effect size. Based on systematic observed differences, large studies assessing DRD with a small number of self-report items were removed and an analysis of 57 comparisons (n=3,329) using equivalent methods and exhibiting acceptable heterogeneity revealed a medium magnitude effect (d= .58; p< .00001). Further analyses revealed significantly larger effect sizes for studies using clinical samples (d= .61) compared with studies using nonclinical samples (d=.45). Indices of small study bias among the various comparisons suggested varying levels of influence by unpublished findings, ranging from minimal to moderate. These results provide strong evidence of greater DRD in individuals exhibiting addictive behavior in general and particularly in individuals who meet criteria for an addictive disorder. Implications for the assessment of DRD and research priorities are discussed.
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                Author and article information

                Contributors
                URI : http://frontiersin.org/people/u/157040
                URI : http://frontiersin.org/people/u/222158
                Journal
                Front Psychiatry
                Front Psychiatry
                Front. Psychiatry
                Frontiers in Psychiatry
                Frontiers Media S.A.
                1664-0640
                08 February 2016
                2015
                : 6
                : 175
                Affiliations
                [1] 1Department of Psychiatry, University of Minnesota , Minneapolis, MN, USA
                [2] 2Program in PharmacoNeuroImmunology, Department of Psychiatry, University of Minnesota , Minneapolis, MN, USA
                Author notes

                Edited by: Liana Fattore, National Research Council (CNR), Italy

                Reviewed by: Marci R. Mitchell, Yale University, USA; Robert F. Leeman, University of Florida, USA

                *Correspondence: Marilyn E. Carroll, mcarroll@ 123456umn.edu

                Specialty section: This article was submitted to Addictive Disorders, a section of the journal Frontiers in Psychiatry

                Article
                10.3389/fpsyt.2015.00175
                4745113
                26903885
                4191e538-d046-4bf3-b1fd-f6c6f4e1e6ad
                Copyright © 2016 Carroll and Smethells.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 15 March 2015
                : 30 November 2015
                Page count
                Figures: 0, Tables: 1, Equations: 0, References: 281, Pages: 20, Words: 20521
                Categories
                Psychiatry
                Review

                Clinical Psychology & Psychiatry
                animal models,behavioral dyscontrol,drug addiction,food addiction,impulsivity,sweet intake,sex differences,novel treatments

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