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Restoring executive control in drug addiction through the disruption on memories
If you have a question about this talk, please contact Hannah Critchlow.
This talk is part of the Cambridge Clinical Neuroscience and Mental Health Symposium, 29th – 30th September 2009 at West Road Concert Hall. This event is free to attend for cambridge neuroscientists although registration is required. To register, and for further information, please visit: http://www.neuroscience.cam.ac.uk/cnmhs/
Abstract: Drug addiction is a chronic disorder that is characterised by compulsive drug use and an extended propensity of addicted individuals to relapse. Several prominent theories of addiction emphasise the loss of control over drug use in addiction, postulating that drug-seeking behaviour becomes dominated by subcortically mediated habitual representations, rather than the goal-directed behaviour mediated by the frontal cortices. These subcortical representations are driven by the presentation of environmental stimuli that have previously been predictive of drug, and therefore relapse to drug-seeking is automatic and unconscious in the presence of these drug-associated stimuli.
The capacity of drug-associated stimuli to activate key limbic areas implicated in relapse has been demonstrated in functional imaging studies, and in animal models of addiction. As drug-associated stimuli are potent precipitators of relapse, any therapy that could disrupt the association between the environmental stimulus (CS) and the drug would be hypothesised to reduce the risk of relapse. This has informed cue-exposure (‘extinction’) therapies, but these have had limited long-term success in treating addiction. An alternative technique is the targeting of memory reconsolidation, the process by which memories require restabilisation following their destabilisation at retrieval.
We have investigated the mechanisms underlying the reconsolidation of CS-drug memories, characterising the dependence of this process upon the NMDA subtype of glutamate receptor, adrenergic receptors and the immediate early gene zif268. We have also deconstructed animal models of relapse in addiction, demonstrating that treatments based upon the disruption of reconsolidation can disrupt all three ways in which pavlovian CSs can influence instrumental relapse behaviour. Therefore, the administration of amnestic agents, in conjunction with a CS-drug memory retrieval session, may provide a novel form of pro-abstinence / anti-relapse therapy for addiction, by reducing the dominance of subcortically-mediated memory representations over behaviour.
References Milton AL, Lee JLC , Butler VJ, Gardner R & Everitt BJ (2008) Intra-amygdala and systemic antagonism of NMDA receptors prevents the reconsolidation of drug-associated memory and impairs subsequently both novel and previously acquired drug-seeking behaviors. J Neurosci 28: 8230-7.
Milton AL, Lee JLC & Everitt BJ (2008) Reconsolidation of appetitive memories for drug reinforcement is dependent on -adrenergic receptors. Learn Mem 15: 88-92.
Lee JLC , Milton AL & Everitt BJ (2006) Cue-induced cocaine seeking and relapse are reduced by disruption of drug memory reconsolidation. J Neurosci 26: 5881-7.
Biosketch: Amy Milton is a Departmental Lecturer in the Behavioural and Clinical Neuroscience Institute, in the Department of Experimental Psychology, University of Cambridge. She graduated from Newnham College, Cambridge, with an M.A. in Neuroscience before undertaking a Ph.D. with Professor Barry Everitt, investigating the neuropharmacological mechanisms that underlie memory processes relevant to drug addiction, obesity, and post-traumatic stress disorder. After completing her doctorate, she became a Research Fellow at Downing College, Cambridge. Her particular research interest is in characterising the neurochemical mechanisms that underlie the reconsolidation of different memory types, with a translational view of applying such knowledge to the development of reconsolidation-based treatments for neuropsychiatric disorders in humans.
This talk is part of the Clinical Neuroscience and Mental Health Symposium series.
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