Selective, Retrieval-Independent Disruption of Methamphetamine-Associated Memory by Actin Depolymerization (2013)

Biol Psychiatry. 2013 Sep 5. pii: S0006-3223(13)00727-0. doi: 10.1016/j.biopsych.2013.07.036.

Young EJ, Aceti M, Griggs EM, Fuchs RA, Zigmond Z, Rumbaugh G, Miller CA.


Department of Metabolism and Aging (EJY, EMG, ZZ, CAM); Department of Neuroscience (EJY, MA, EMG, ZZ, GR, CAM), The Scripps Research Institute, Jupiter, Florida.



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.


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.


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.


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.

© 2013 Society of Biological Psychiatry.

Selectively erasing unwanted memories

September 13, 2013

Scientists from the Florida campus of The Scripps Research Institute (TSRI) have been able to erase dangerous drug-associated memories in mice and rats without affecting other more benign memories.

The surprising discovery points to a clear and workable method to disrupt unwanted memories while leaving the rest intact, the scientists say.

For recovering addicts and individuals suffering from post-traumatic stress disorder (PTSD), unwanted memories can be devastating. Former meth addicts, for instance, report intense drug cravings triggered by associations with cigarettes, money, even gum (used to relieve dry mouth), pushing them back into the addiction they so desperately want to leave.

As in the movie Eternal Sunshine of the Spotless Mind (a couple undergo a procedure to erase each other from their memories when their relationship turns sour), “we’re looking for strategies to selectively eliminate evidence of past experiences related to drug abuse or a traumatic event.

“Our study shows we can do just that in mice — wipe out deeply engrained drug-related memories without harming other memories,” said Courtney Miller, a TSRI assistant professor who led the research.

How to change memories

  1. Mice and rats were first trained to associate the rewarding effects of methamphetamine with a rich context of visual, tactile and scent cues.
  2. The scientists later inhibited actin polymerization — the creation of large chainlike molecules — by blocking a molecular motor called myosin II in their brains during the maintenance phase of methamphetamine-related memory formation. (To produce a memory, a lot has to happen, including the alteration of the structure of nerve cells via changes in the dendritic spines — small bulb-like structures that receive electrochemical signals from other neurons. Normally, these structural changes occur via actin, the protein that makes up the infrastructure of all cells.)
  3. Behavioral tests showed the animals immediately and persistently lost memories associated with methamphetamine. At the same time, the response to other memories, such as food rewards, was unaffected.

The scientists are not yet sure why powerful methamphetamine-related memories are also so fragile, but they think it could be related to the role of dopamine, a neurotransmitter involved in reward and pleasure centers in the brain. Dopamine is released during both learning and drug withdrawal.

“The hope is that our strategies may be applicable to other harmful memories, such as those that perpetuate smoking or PTSD,” Miller said.

The research was supported by the National Institute on Drug Abuse and the National Institute for Neurological Disorders and Stroke.


    Erica J. Young et al., Selective, Retrieval-Independent Disruption of Methamphetamine-Associated Memory by Actin Depolymerization, Biological Psychiatry, 2013, DOI: 10.1016/j.biopsych.2013.07.036

Topics: Cognitive Science/Neuroscience