Neural substrates of drug craving and relapse in drug addiction

Research output: Contribution to journalArticle

105 Citations (Scopus)

Abstract

Drug addiction is characterized by motivational disturbances such as compulsive drug taking and episodes of intense drug craving. Recent advances using animal models of relapse have shown that drug-seeking behaviour can be triggered by drug-associated cues, by stress and by 'priming' injections of the drugs themselves, events also known to trigger drug craving in human drug addicts. Current evidence suggests that these stimuli all induce relapse, at least in part, by their common ability to activate the mesolimbic dopamine system. Drug-associated cues and stress can activate this system via neural circuits from the prefrontal cortex and amygdala and through activation of the hypothalamic-pituitary-adrenal axis. Our studies suggest that dopamine triggers relapse to drug-seeking behaviour by stimulating D2-dopamine receptors which inhibit the cyclic AMP second messenger pathway in the neurones of the nucleus accumbens. In contrast, compounds which activate D1 receptors prevent relapse to drug-seeking behaviour, possibly through satiation of reward pathways. Chronic neuroadaptations in dopamine receptor signalling pathways in the nucleus accumbens caused by repeated drug use are hypothesized to produce tolerance to the rewarding effects of D1-receptor stimulation, leading to increased drug intake during drug self-administration. Conversely, these same neuroadaptations are hypothesized to enhance drug craving by potentiating D2 receptor-mediated signals during abstinence. These findings identify D1 and D2-dopamine receptor mechanisms as potential targets for developing anticraving compounds to treat drug addiction.

Original languageEnglish (US)
Pages (from-to)379-389
Number of pages11
JournalAnnals of Medicine
Volume30
Issue number4
StatePublished - 1998

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Substance-Related Disorders
Recurrence
Pharmaceutical Preparations
Drug-Seeking Behavior
Dopamine D2 Receptors
Nucleus Accumbens
Cues
Dopamine
Craving
Satiation
Dopamine D1 Receptors
Aptitude
Self Administration
Dopamine Receptors
Second Messenger Systems
Drug Users
Amygdala
Prefrontal Cortex
Reward
Cyclic AMP

Keywords

  • Addiction
  • Cocaine
  • Craving
  • Dopamine
  • Nucleus accumbens
  • Reinstatement

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Neural substrates of drug craving and relapse in drug addiction. / Self, David W.

In: Annals of Medicine, Vol. 30, No. 4, 1998, p. 379-389.

Research output: Contribution to journalArticle

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