ReviewNeurobiological substrates for the dark side of compulsivity in addiction
Section snippets
Definitions and conceptual framework for compulsivity in addiction
Drug addiction is a chronically relapsing disorder characterized by (i) compulsion to seek and take the drug, (ii) loss of control in limiting intake, and (iii) emergence of a negative emotional state (e.g., dysphoria, anxiety, irritability) reflecting a motivational withdrawal syndrome when access to the drug is prevented (defined here as dependence) (Koob and Le Moal, 1997). Addiction is assumed to be identical to the syndrome of substance dependence (as currently defined by the Diagnostic
Within-system neuroadaptations that contribute to the negative emotional state component of compulsivity
Within-system neuroadaptations to chronic drug exposure include decreases in function of the same neurotransmitter systems in the same neurocircuits implicated in the acute reinforcing effects of drugs of abuse. One prominent hypothesis is that dopamine systems are compromised in crucial phases of the addiction cycle, such as withdrawal and leads to decreased motivation for non-drug-related stimuli and increased sensitivity to the abused drug (Melis et al., 2005). Activation of the mesolimbic
Within-system neuroadaptations
In a series of studies, dopamine partial agonists have not only been shown to reverse psychostimulant withdrawal but also to block the increase in psychostimulant self-administration associated with extended access. Dopamine partial agonists decrease the reinforcing effects of psychostimulant drugs in non-dependent limited access paradigms (Izzo et al., 2001, Pulvirenti et al., 1998). However, animals with extended access show an increased sensitivity to a dopamine partial agonist (Wee et al.,
Compulsivity in addiction: an allostatic view
Compulsivity in addiction can derive from multiple sources, including enhanced incentive salience, engagement of habit function, and impairment in executive function. However, underlying each of these sources is a negative emotional state that may strongly impact on compulsivity. The development of the negative emotional state that drives the negative reinforcement of addiction has been defined as the “dark side” of addiction (Koob and Le Moal, 2005, Koob and Le Moal, 2008) and is hypothesized
Acknowledgments
The author would like to thank Michael Arends and Mellany Santos for their outstanding assistance with the preparation of this manuscript. Research was supported by National Institutes of Health grants AA06420 and AA08459 from the National Institute on Alcohol Abuse and Alcoholism, DA10072, DA04043, and DA04398 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 Center for
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