Abstract
Relapse to alcohol abuse is an important clinical issue that is frequently caused by cue-induced drug craving. Therefore, disruption of the memory for the cue-alcohol association is expected to prevent relapse. It is increasingly accepted that memories become labile and erasable soon after their reactivation through retrieval during a memory reconsolidation process that depends on protein synthesis. Here we show that reconsolidation of alcohol-related memories triggered by the sensory properties of alcohol itself (odor and taste) activates mammalian target of rapamycin complex 1 (mTORC1) in select amygdalar and cortical regions in rats, resulting in increased levels of several synaptic proteins. Furthermore, systemic or central amygdalar inhibition of mTORC1 during reconsolidation disrupts alcohol-associated memories, leading to a long-lasting suppression of relapse. Our findings provide evidence that the mTORC1 pathway and its downstream substrates are crucial in alcohol-related memory reconsolidation and highlight this pathway as a therapeutic target to prevent relapse.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Amygdala / drug effects
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Amygdala / physiopathology*
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Animals
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Anisomycin / pharmacology*
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Anisomycin / therapeutic use
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Binge Drinking / prevention & control
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Binge Drinking / psychology*
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Conditioning, Operant / physiology
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Cues
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Ethanol / blood
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Ethanol / chemistry
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Ethanol / pharmacology
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Male
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Mechanistic Target of Rapamycin Complex 1
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Memory / drug effects*
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Memory / physiology
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Multiprotein Complexes / antagonists & inhibitors*
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Multiprotein Complexes / physiology
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Nerve Tissue Proteins / biosynthesis
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Nerve Tissue Proteins / genetics
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Neuronal Plasticity
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Odorants
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Phosphorylation / drug effects
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Prefrontal Cortex / drug effects
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Prefrontal Cortex / physiopathology*
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Protein Biosynthesis / drug effects
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Protein Biosynthesis / physiology
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Protein Processing, Post-Translational / drug effects
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Rats
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Rats, Long-Evans
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Signal Transduction / drug effects
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Signal Transduction / physiology
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Sirolimus / pharmacology*
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Sirolimus / therapeutic use
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Spatial Behavior / drug effects
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Spatial Behavior / physiology
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TOR Serine-Threonine Kinases / antagonists & inhibitors*
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TOR Serine-Threonine Kinases / physiology
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Taste
Substances
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Multiprotein Complexes
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Nerve Tissue Proteins
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Ethanol
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Anisomycin
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Mechanistic Target of Rapamycin Complex 1
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TOR Serine-Threonine Kinases
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Sirolimus