Journal
PHARMACOPSYCHIATRY
Volume 42, Issue -, Pages S32-S41Publisher
GEORG THIEME VERLAG KG
DOI: 10.1055/s-0029-1216356
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Funding
- National Institutes of Health [AA06420, AA08459]
- National Institute on Alcohol Abuse and Alcoholism
- National Institute on Drug Abuse [DA10072, DA04043, DA04398]
- National Institute of Diabetes and Digestive and Kidney Diseases [DK26741]
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [P01DK026741] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM [R37AA008459, R01AA008459, P50AA006420, P60AA006420] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON DRUG ABUSE [R01DA010072, R01DA004398, R01DA004043] Funding Source: NIH RePORTER
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Drug addiction is conceptualized as chronic, relapsing compulsive use of drugs with significant dysregulation of brain hedonic systems. Compulsive drug use is accompanied by decreased function of brain substrates for drug positive reinforcement and recruitment of brain substrates mediating the negative reinforcement of motivational withdrawal, The neural substrates for motivational withdrawal (dark side of addiction) involve recruitment of elements of the extended amygdala and the brain stress systems, including corticotropin-releasing factor and norepinephrine. These changes, combined with decreased reward function, are hypothesized to persist in the form of an allostatic state that forms a powerful motivational background for relapse. Relapse also involves a key role for the basolateral amygdala in mediating the motivational effects of stimuli previously paired with drug seeking and drug motivational withdrawal. The basolateral amygdala has a key role in mediating emotional memories in general. The hypothesis argued here is that brain stress systems activated by the motivational consequences of drug withdrawal can not only form the basis for negative reinforcement that drives drug seeking, but also potentiate associative mechanisms that perpetuate the emotional state and help drive the allostatic state of addiction.
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