Bidirectional modulation of alcohol-associated memory reconsolidation through manipulation of adrenergic signaling
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Schramm, M. J., Everitt, B., & Milton, A. (2015). Bidirectional modulation of alcohol-associated memory reconsolidation through manipulation of adrenergic signaling. Neuropsychopharmacology, 41 1103-1111. https://doi.org/10.1038/npp.2015.248
Alcohol addiction is a problem of great societal concern, for which there is scope to improve current treatments. One potential new treatment for alcohol addiction is based on disrupting the reconsolidation of the maladaptive Pavlovian memories that can precipitate relapse to drug-seeking behavior. In alcohol self-administering rats, we investigated the effects of bidirectionally modulating adrenergic signaling on the strength of a Pavlovian cue-alcohol memory, using a behavioral procedure that isolates the specific contribution of one maladaptive Pavlovian memory to relapse, the acquisition of a new alcohol-seeking response for an alcohol-associated conditioned reinforcer. The β-adrenergic receptor antagonist propranolol, administered in conjunction with memory reactivation, persistently disrupted the memory that underlies the capacity of a previously alcohol-associated cue to act as a conditioned reinforcer. By contrast, enhancement of adrenergic signaling by administration of the adrenergic prodrug dipivefrin at reactivation increased the strength of the cue-alcohol memory and potentiated alcohol seeking. These data demonstrate the importance of adrenergic signaling in alcohol-associated memory reconsolidation, and suggest a pharmacological target for treatments aiming to prevent relapse through the disruption of maladaptive memories.
This work was supported by a UK Medical Research Council Programme Grant (G1002231) to BJE and ALM and was conducted in the Behavioural and Clinical Neuroscience Institute (BCNI), an initiative jointly funded by the MRC and the Wellcome Trust. MJWS was supported by an MRC Doctoral Training Grant and the James Baird Fund at the Medical School of the University of Cambridge. ALM was partly supported by a BCNI lectureship and the Ferreras-Willetts Fellowship from Downing College, Cambridge.
MEDICAL RESEARCH COUNCIL (G0001354)
Wellcome Trust (093875/Z/10/Z)
External DOI: https://doi.org/10.1038/npp.2015.248
This record's URL: https://www.repository.cam.ac.uk/handle/1810/249304