Invited reviewAddiction as a stress surfeit disorder
Section snippets
Conceptual framework for the dark side of addiction
Addiction has been conceptualized as a three-stage cycle—binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation—with two primary sources of reinforcement: positive and negative reinforcement. Positive reinforcement is defined as the process by which presentation of a stimulus increases the probability of a response; negative reinforcement is defined as the process by which removal of an aversive stimulus (or aversive state in the case of addiction) increases the
Brain stress systems
The brain stress systems can be defined as neurochemical systems that are activated during exposure to acute stressors or in a chronic state of stress and mediate species-typical behavioral responses. These behavioral responses in animals range from freezing to flight and typically have face and predictive validity for similar behavior responses in humans. For example, animals exposed to a stressor will show an enhanced freezing response to a conditioned fear stimulus, an enhanced startle
Corticotropin-releasing factor, compulsive-like drug seeking, and the extended amygdala
The ability of CRF antagonists to block the anxiogenic-like and aversive-like motivational effects of drug withdrawal predicted motivational effects of CRF antagonists in animal models of extended access to drugs. CRF antagonists selectively blocked the increased self-administration of drugs associated with extended access to intravenous self-administration of cocaine (Specio et al., 2008), nicotine (George et al., 2007), and heroin (Greenwell et al., 2009; Fig. 4). For example, systemic
Brain stress systems in addiction: an allostatic view
For the binge/intoxication stage of the addiction cycle, studies of the acute reinforcing effects of drugs of abuse per se have identified key neurobiological substrates. Evidence is strong for a role for dopamine in the acute reinforcing actions of psychostimulants, opioid peptide receptors in the acute reinforcing effects of opioids, and GABA and opioid peptides in the acute reinforcing actions of alcohol. Important anatomical circuits include the mesocorticolimbic dopamine system that
Acknowledgments
The author would like to thank Michael Arends and Mellany Santos for their assistance with the preparation of this manuscript. Research was supported by National Institutes of Health grants AA006420, AA020608, and AA008459 from the National Institute on Alcohol Abuse and Alcoholism, DA010072, DA004043, DA023597, and DA004398 from the National Institute on Drug Abuse, and DK26741 from the National Institute of Diabetes and Digestive and Kidney Diseases. Research also was supported by the Pearson
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