title: Selective, retrieval-independent disruption of methamphetamine-associated memory by actin depolymerization.
abstract: BACKGROUND
  Memories associated with drugs of abuse, such as methamphetamine (METH), increase relapse vulnerability to substance use disorder. There is a growing consensus that memory is supported by structural and functional plasticity driven by F-actin polymerization in postsynaptic dendritic spines at excitatory synapses. However, the mechanisms responsible for the long-term maintenance of memories, after consolidation has occurred, are largely unknown.
  
  
  METHODS
  Conditioned place preference (n = 112) and context-induced reinstatement of self-administration (n = 19) were used to assess the role of F-actin polymerization and myosin II, a molecular motor that drives memory-promoting dendritic spine actin polymerization, in the maintenance of METH-associated memories and related structural plasticity.
  
  
  RESULTS
  Memories formed through association with METH but not associations with foot shock or food reward were disrupted by a highly-specific actin cycling inhibitor when infused into the amygdala during the postconsolidation maintenance phase. This selective effect of depolymerization on METH-associated memory was immediate, persistent, and did not depend upon retrieval or strength of the association. Inhibition of non-muscle myosin II also resulted in a disruption of METH-associated memory.
  
  
  CONCLUSIONS
  Thus, drug-associated memories seem to be actively maintained by a unique form of cycling F-actin driven by myosin II. This finding provides a potential therapeutic approach for the selective treatment of unwanted memories associated with psychiatric disorders that is both selective and does not rely on retrieval of the memory. The results further suggest that memory maintenance depends upon the preservation of polymerized actin.
authors.affiliation: Department of Metabolism and Aging, The Scripps Research Institute, Jupiter, Florida; Department of Neuroscience, The Scripps Research Institute, Jupiter, Florida.
authors.forename: Erica J
authors.initials: EJ
authors.lastname: Young
authors.affiliation: Department of Neuroscience, The Scripps Research Institute, Jupiter, Florida.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Aceti
authors.affiliation: Department of Metabolism and Aging, The Scripps Research Institute, Jupiter, Florida; Department of Neuroscience, The Scripps Research Institute, Jupiter, Florida.
authors.forename: Erica M
authors.initials: EM
authors.lastname: Griggs
authors.affiliation: Department of Psychology, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Rita A
authors.initials: RA
authors.lastname: Fuchs
authors.affiliation: Department of Metabolism and Aging, The Scripps Research Institute, Jupiter, Florida; Department of Neuroscience, The Scripps Research Institute, Jupiter, Florida.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Zigmond
authors.affiliation: Department of Neuroscience, The Scripps Research Institute, Jupiter, Florida.
authors.forename: Gavin
authors.initials: G
authors.lastname: Rumbaugh
authors.affiliation: Department of Metabolism and Aging, The Scripps Research Institute, Jupiter, Florida; Department of Neuroscience, The Scripps Research Institute, Jupiter, Florida. Electronic address: cmiller@scripps.edu.
authors.forename: Courtney A
authors.initials: CA
authors.lastname: Miller
mesh_terms: D000199:Actins / Q000187:drug effects / Q000378:metabolism*; D000679:Amygdala / Q000187:drug effects; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D003213:Conditioning, Psychological / Q000187:drug effects*; D049229:Dendritic Spines / Q000187:drug effects; D004558:Electric Stimulation; D005108:Extinction, Psychological / Q000187:drug effects; D005502:Food; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000187:drug effects*; D011939:Mental Recall / Q000187:drug effects*; D008694:Methamphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008845:Microinjections; D024462:Myosin Type II / Q000187:drug effects / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects; D058105:Polymerization / Q000187:drug effects; D051381:Rats; D012201:Reward; D012646:Self Administration; D053778:Thiazolidines / Q000494:pharmacology
chemical_list: D000199:Actins; D019086:Bridged Bicyclo Compounds, Heterocyclic; D006576:Heterocyclic Compounds, 4 or More Rings; D053778:Thiazolidines; C472645:blebbistatin; D008694:Methamphetamine; D024462:Myosin Type II; C037067:latrunculin A
keywords: Addiction; amygdala; dendritic spine; memory maintenance; myosin; structural plasticity