Selective, retrieval-independent disruption of methamphetamine-associated memory by actin depolymerization

Biol Psychiatry. 2014 Jan 15;75(2):96-104. doi: 10.1016/j.biopsych.2013.07.036. Epub 2013 Sep 5.


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.

Keywords: Addiction; amygdala; dendritic spine; memory maintenance; myosin; structural plasticity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Actins / drug effects
  • Actins / metabolism*
  • Amygdala / drug effects
  • Animals
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology
  • Conditioning, Psychological / drug effects*
  • Dendritic Spines / drug effects
  • Electric Stimulation
  • Extinction, Psychological / drug effects
  • Food
  • Heterocyclic Compounds, 4 or More Rings / pharmacology
  • Male
  • Memory / drug effects*
  • Mental Recall / drug effects*
  • Methamphetamine / administration & dosage
  • Methamphetamine / pharmacology*
  • Mice
  • Microinjections
  • Myosin Type II / drug effects
  • Myosin Type II / metabolism
  • Neuronal Plasticity / drug effects
  • Polymerization / drug effects
  • Rats
  • Reward
  • Self Administration
  • Thiazolidines / pharmacology


  • Actins
  • Bridged Bicyclo Compounds, Heterocyclic
  • Heterocyclic Compounds, 4 or More Rings
  • Thiazolidines
  • blebbistatin
  • Methamphetamine
  • Myosin Type II
  • latrunculin A