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Review
. 2008 Oct 12;363(1507):3147-58.
doi: 10.1098/rstb.2008.0084.

Review. Psychological and neural mechanisms of relapse

Jane Stewart  1
Affiliations
Review

Review. Psychological and neural mechanisms of relapse

Jane Stewart. Philos Trans R Soc Lond B Biol Sci. .

Abstract

Relapse, the resumption of drug taking after periods of abstinence, remains the major problem for the treatment of addiction. Even when drugs are unavailable for long periods or when users are successful in curbing their drug use for extended periods, individuals remain vulnerable to events that precipitate relapse. Behavioural studies in humans and laboratory animals show that drug-related stimuli, drugs themselves and stressors are powerful events for the precipitation of relapse. Molecular, neurochemical and anatomical studies have identified lasting neural changes that arise from mere exposure to drugs and other enduring changes that arise from learning about the relationship between drug-related stimuli and drug effects. Chronic drug exposure increases sensitivity of some systems of the brain to the effects of drugs and stressful events. These changes, combined with those underlying conditioning and learning, perpetuate vulnerability to drug-related stimuli. Circuits of the brain involved are those of the mesocorticolimbic dopaminergic system and its glutamatergic connections, and the corticotropin-releasing factor and noradrenergic systems of the limbic brain. This paper reviews advances in our understanding of how these systems mediate the effects of events that precipitate relapse and of how lasting changes in these systems can perpetuate vulnerability to relapse.

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Figures

Figure 1
Figure 1
Diagram showing the primary circuits and neurotransmitters implicated in drug-induced reinstatement. VTA, ventral tegmental area, cell body regions of mesocorticolimbic DA pathway; NAc, nucleus accumbens; mPFC, medial prefrontal cortex; VP/SNr, ventral pallidum/substantia nigra reticulata; PPT/LDT, peduncular pontine and laterodorsal tegmental nuclei. Grey, dopamine; black, glutamate.
Figure 2
Figure 2
Diagram showing the primary circuits and neurotransmitters implicated in cue-induced reinstatement. VTA, ventral tegmental area, cell body regions of mesocorticolimbic DA pathway; NAc, nucleus accumbens; mPFC, medial prefrontal cortex; VP/SNr, ventral pallidum/substantia nigra reticulata; PPT/LDT, peduncular pontine and laterodorsal tegmental nuclei; BLA, basolateral amygdala; HIPP, hippocampus. Grey, dopamine; black, glutamate.
Figure 3
Figure 3
Diagram showing the primary circuits and neurotransmitters implicated in stress-induced reinstatement. VTA, ventral tegmental area, cell body regions of mesocorticolimbic DA pathway; NAc, nucleus accumbens; mPFC, medial prefrontal cortex; VP/SNr, ventral pallidum/substantia nigra reticulata; PPT/LDT, peduncular pontine and laterodorsal tegmental nuclei; BLA, basolateral amygdala; HIPP, hippocampus; CeA, central nucleus of the amygdala; BNST, bed nucleus of the stria terminalis. Dark grey, dopamine; black, glutamate; light grey, CRF.
Figure 4
Figure 4
Diagram showing the primary circuits and neurotransmitters implicated in reinstatement by drugs, cues and stressors. VTA, ventral tegmental area, cell body regions of mesocorticolimbic DA pathway; NAc, nucleus accumbens; mPFC, medial prefrontal cortex; VP/SNr, ventral pallidum/substantia nigra reticulata; PPT/LDT, peduncular pontine and laterodorsal tegmental nuclei; BLA, basolateral amygdala; HIPP, hippocampus; CeA, central nucleus of the amygdala; BNST, bed nucleus of the stria terminalis; LTN, lateral tegmental nuclei; NA, noradrenaline. Dark grey, dopamine; black, glutamate; light grey, CRF; black dots, noradrenaline.
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