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Chapter 49. Neurobiology of Substance Abuse and Addiction

Ashley P. Kennedy, B.S.; Clinton D. Kilts, Ph.D.
DOI: 10.1176/appi.books.9781585623860.433008

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Excerpt

Drug addiction is characterized by pathological motivation for drug-seeking and -use behaviors associated with the inability to inhibit such behaviors in spite of their clear adverse consequences (Kalivas and Volkow 2005). These features are clinically operationalized as a diagnosis of drug dependence based on an individual's fulfilling at least three of seven criteria defined by DSM-IV-TR (American Psychiatric Association 2000). The authors conform to the position (O'Brien et al. 2006) that drug addiction rather than dependence is more appropriate in referring to this maladaptive behavioral disorder and refer to drug dependence only when referring to clinical populations defined by DSM-IV-TR criteria. Drug addiction represents a major public health concern due to its high population prevalence, associated suffering and disability, and limited efficacy of extant therapies to promote recovery and relapse prevention. Understanding the underlying neurobiology of drug abuse and addiction offers the best promise to control drug addiction by identifying the bases of risk for addiction and targeting intervention strategies, uncoupling relapse from its precipitants, and minimizing the personal and social burden of addiction. This chapter represents a critical review of the current state of this understanding and a synthesis of knowledge into present and future directives for managing drug abuse and addiction. The treatment here of this topic is not meant to be comprehensive, but rather focuses on the authors' prioritization of those scientific areas of discovery that are perceived to be most relevant to curbing drug addiction. Attempts have been made to direct interested readers to more exhaustive treatments of less prioritized areas of addiction research findings.

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FIGURE 49–1. Theoretical model of the causes and consequences of drug addiction.A three-stage model is proposed that entails the addiction process from initial drug use, the transition to chronic drug abuse and addiction, the chronically relapsing nature of addiction, and the social and personal costs of end-stage addiction. The roles of learning, memory, reward sensitivity, and emotion regulation are highlighted. Factors that positively and negatively modulate the addiction acquisition stage are shown. Psychosocial factors include the influence of peers, family, cultural variables, social and religious beliefs, socioeconomic status, drug attitudes, and the illicit versus licit nature of the drug of abuse. Genetic factors include allelic and haplotypic variation for genes regulating cognitive functions, drug pharmacokinetics and pharmacodynamics, and personality traits. Neurodevelopmental factors include risks posed by the adolescent period and by childhood maltreatment. Brain anatomical and neurotransmitter substrates are proposed for the different stages of the addiction process. CRF = corticotropin-releasing factor; OFC = orbitofrontal cortex; SES = socioeconomic status.

FIGURE 49–2. Models of neurobiological mechanisms of relapse to drug seeking and drug use.To elucidate the emerging neurobiology of mechanisms of relapse to drug-seeking and -use behaviors associated with drug addiction, we consider and compare three potential precipitants of relapse: conditioned drug-use reminders or cues (A, Cue-induced relapse model), stress (B, Stress-induced relapse model), and use/administration of the drug itself (C, Drug-induced relapse model). For each model presented, the neuroanatomical areas and neurotransmitter mechanisms involved (as defined by investigation of the reinstatement animal model of relapse) are shown on the right, and the distributed neural processing associated with experiencing the relapse precipitant (as defined by human in vivo functional neuroimaging studies in males) is shown on the left. It should be emphasized that these neurobiological mechanisms reflect major but not all research findings and represent an as-yet-incomplete characterization of the mechanisms of relapse. Therefore, strict comparisons of the underlying mechanisms between the three relapse precipitants should be done with caution.ACC = anterior cingulate cortex; Amyg = amygdala; BLA = basolateral amygdaloid nucleus; BNST = bed nucleus of the stria terminalis; CB = cerebellum; CE = central amygdaloid nucleus; CRF = corticotropin-releasing factor; CRF1R = corticotropin-releasing factor 1 receptor; CRF2R = corticotropin-releasing factor 2 receptor; D3R = D3 dopamine receptor; dACC = dorsal anterior cingulate cortex; dlPFC = dorsolateral prefrontal cortex; dStr = dorsal striatum; HC = hippocampus; Ins = insula; lOFC = left orbitofrontal cortex; mCC = middle cingulate cortex; MTG = medial temporal gyrus; Nac = nucleus accumbens; OFC = orbitofrontal cortex; pCC = posterior cingulate cortex; PFC = prefrontal cortex; VIS = visual cortex; VP = ventral pallidum; vStr = ventral striatum; VTM = ventral tegmentum.
Table Reference Number
TABLE 49–1. Stages of the addiction process targeted by addiction therapies

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With regard to cocaine abuse in the United States, there are significant sex differences in patterns of abuse and in their treatment. Which of the following statements is true?
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What environmental factor has been reported in more than half of drug abusers entering a drug addiction treatment program?
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