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      The dark side of emotion: the addiction perspective

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          Abstract

          Emotions are “feeling” states and classic physiological emotive responses that are interpreted based on the history of the organism and the context. Motivation is a persistent state that leads to organized activity. Both are intervening variables and intimately related and have neural representations in the brain. The present thesis is that drugs of abuse elicit powerful emotions that can be interwoven conceptually into this framework. Such emotions range from pronounced euphoria to a devastating negative emotional state that in the extreme can create a break with homeostasis and thus an allostatic hedonic state that has been considered key to the etiology and maintenance of the pathophysiology of addiction. Drug addiction can be defined as a three-stage cycle— binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation—that involves allostatic changes in the brain reward and stress systems. Two primary sources of reinforcement, positive and negative reinforcement, have been hypothesized to play a role in this allostatic process. The negative emotional state that drives negative reinforcement is hypothesized to derive from dysregulation of key neurochemical elements involved in the brain incentive salience and stress systems. Specific neurochemical elements in these structures include not only decreases in incentive salience system function in the ventral striatum (within-system opponent processes) but also recruitment of the brain stress systems mediated by corticotropin-releasing factor (CRF), dynorphin-κ opioid systems, and norepinephrine, vasopressin, hypocretin, and substance P in the extended amygdala (between-system opponent processes). Neuropeptide Y, a powerful anti-stress neurotransmitter, has a profile of action on compulsive-like responding for drugs similar to a CRF 1 antagonist. Other stress buffers include nociceptin and endocannabinoids, which may also work through interactions with the extended amygdala. The thesis argued here is that the brain has specific neurochemical neurocircuitry coded by the hedonic extremes of pleasant and unpleasant emotions that have been identified through the study of opponent processes in the domain of addiction. These neurochemical systems need to be considered in the context of the framework that emotions involve the specific brain regions now identified as differentially interpreting emotive physiological expression.

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          Diagnostic and statistical manual of mental disorders.

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            The neural basis of drug craving: an incentive-sensitization theory of addiction.

            This paper presents a biopsychological theory of drug addiction, the 'Incentive-Sensitization Theory'. The theory addresses three fundamental questions. The first is: why do addicts crave drugs? That is, what is the psychological and neurobiological basis of drug craving? The second is: why does drug craving persist even after long periods of abstinence? The third is whether 'wanting' drugs (drug craving) is attributable to 'liking' drugs (to the subjective pleasurable effects of drugs)? The theory posits the following. (1) Addictive drugs share the ability to enhance mesotelencephalic dopamine neurotransmission. (2) One psychological function of this neural system is to attribute 'incentive salience' to the perception and mental representation of events associated with activation of the system. Incentive salience is a psychological process that transforms the perception of stimuli, imbuing them with salience, making them attractive, 'wanted', incentive stimuli. (3) In some individuals the repeated use of addictive drugs produces incremental neuroadaptations in this neural system, rendering it increasingly and perhaps permanently, hypersensitive ('sensitized') to drugs and drug-associated stimuli. The sensitization of dopamine systems is gated by associative learning, which causes excessive incentive salience to be attributed to the act of drug taking and to stimuli associated with drug taking. It is specifically the sensitization of incentive salience, therefore, that transforms ordinary 'wanting' into excessive drug craving. (4) It is further proposed that sensitization of the neural systems responsible for incentive salience ('for wanting') can occur independently of changes in neural systems that mediate the subjective pleasurable effects of drugs (drug 'liking') and of neural systems that mediate withdrawal. Thus, sensitization of incentive salience can produce addictive behavior (compulsive drug seeking and drug taking) even if the expectation of drug pleasure or the aversive properties of withdrawal are diminished and even in the face of strong disincentives, including the loss of reputation, job, home and family. We review evidence for this view of addiction and discuss its implications for understanding the psychology and neurobiology of addiction.
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              Diagnostic and statistical manual of mental disorders

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                Author and article information

                Contributors
                Journal
                1254354
                3614
                Eur J Pharmacol
                Eur. J. Pharmacol.
                European journal of pharmacology
                0014-2999
                1879-0712
                26 February 2015
                09 January 2015
                15 April 2015
                15 April 2016
                : 753
                : 73-87
                Affiliations
                Director, National Institute on Alcohol Abuse and Alcoholism, Washington DC (on leave of absence from Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA)
                Author notes
                [* ]Correspondence: George F. Koob, National Institute on Alcohol Abuse and Alcoholism, 5635 Fishers Lane, Room 2001, Suite 2000, Rockville, MD 20852, tel: 301-443-3885, fax: 301-443-7043, george.koob@ 123456nih.gov
                Article
                NIHMS661974
                10.1016/j.ejphar.2014.11.044
                4380644
                25583178
                76217ca6-fa0e-4d73-8749-2668ab965b65
                © 2015 Published by Elsevier B.V.

                This manuscript version is made available under the CC BY-NC-ND 4.0 license.

                History
                Categories
                Article

                Pharmacology & Pharmaceutical medicine
                opponent process,extended amygdala,corticotropin-releasing factor,dynorphin,incentive salience,emotion,allostasis

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