Bidirectional Modulation of Alcohol-Associated Memory Reconsolidation through Manipulation of Adrenergic Signaling.
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.
Department of Psychology, University of Cambridge, Cambridge, UK.
Moritz J W
MJ
Schramm
Department of Psychology, University of Cambridge, Cambridge, UK.
Barry J
BJ
Everitt
Department of Psychology, University of Cambridge, Cambridge, UK.
Amy L
AL
Milton
D000322:Adrenergic Agonists / Q000008:administration & dosage; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage; D000818:Animals; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology*; D003463:Cues; D058999:Drug-Seeking Behavior / Q000187:drug effects / Q000502:physiology*; D004837:Epinephrine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000431:Ethanol / Q000008:administration & dosage*; D008297:Male; D000069077:Memory Consolidation / Q000187:drug effects / Q000502:physiology*; D009248:Nadolol / Q000008:administration & dosage; D011433:Propranolol / Q000008:administration & dosage; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D012054:Reinforcement, Psychology; D012646:Self Administration
D000322:Adrenergic Agonists; D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D000431:Ethanol; D009248:Nadolol; C015173:dipivefrin; D011433:Propranolol; D004837:Epinephrine