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Response of the Ubiquitin-Proteasome System to Memory Retrieval After Extended-Access Cocaine or Saline Self-Administration
Neuropsychopharmacology (2015)
  • Craig T Werner, Rosalind Franklin University of Medicine and Science
  • Mike Milovanovic, Rosalind Franklin University of Medicine and Science
  • Daniel T Christian, Rosalind Franklin University of Medicine and Science
  • Jessica A Loweth, Rowan University School of Osteopathic Medicine
  • Marina E Wolf, Rosalind Franklin University of Medicine and Science
Abstract
The ubiquitin-proteasome system (UPS) has been implicated in the retrieval-induced destabilization of cocaine- and fear-related memories in Pavlovian paradigms. However, nothing is known about its role in memory retrieval after self-administration of cocaine, an operant paradigm, or how the length of withdrawal from cocaine may influence retrieval mechanisms. Here, we examined UPS activity after an extended-access cocaine self-administration regimen that leads to withdrawal-dependent incubation of cue-induced cocaine craving. Controls self-administered saline. In initial experiments, memory retrieval was elicited via a cue-induced seeking/retrieval test on withdrawal day (WD) 50–60, when craving has incubated. We found that retrieval of cocaine- and saline-associated memories produced similar increases in polyubiquitinated proteins in the nucleus accumbens (NAc), compared with rats that did not undergo a seeking/retrieval test. Measures of proteasome catalytic activity confirmed similar activation of the UPS after retrieval of saline and cocaine memories. However, in a subsequent experiment in which testing was conducted on WD1, proteasome activity in the NAc was greater after retrieval of cocaine memory than saline memory. Analysis of other brain regions confirmed that effects of cocaine memory retrieval on proteasome activity, relative to saline memory retrieval, depend on withdrawal time. These results, combined with prior studies, suggest that the relationship between UPS activity and memory retrieval depends on training paradigm, brain region, and time elapsed between training and retrieval. The observation that mechanisms underlying cocaine memory retrieval change depending on the age of the memory has implications for development of memory destabilization therapies for cue-induced relapse in cocaine addicts.
Keywords
  • Cocaine,
  • Cocaine-Related Disorders,
  • Operant Conditioning,
  • Craving,
  • Cues,
  • Disease Models,
  • Dopamine Uptake Inhibitors,
  • Drug-Seeking Behavior,
  • Memory,
  • Nucleus Accumbens,
  • Proteasome Endopeptidase Complex,
  • Self- Administration,
  • Substance Withdrawal Syndrome,
  • Ubiquitin
Publication Date
January 12, 2015
DOI
10.1038/npp.2015.156
Citation Information
Craig T Werner, Mike Milovanovic, Daniel T Christian, Jessica A Loweth, et al.. "Response of the Ubiquitin-Proteasome System to Memory Retrieval After Extended-Access Cocaine or Saline Self-Administration" Neuropsychopharmacology Vol. 40 Iss. 13 (2015) p. 3006 - 3014 ISSN: 1740-634X (online)
Available at: http://works.bepress.com/jessica-loweth/6/