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Related Experiment Video

Updated: Feb 17, 2026

Assessment of Cocaine-induced Behavioral Sensitization and Conditioned Place Preference in Mice
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Proteasome phosphorylation regulates cocaine-induced sensitization.

Frankie R Gonzales1, Kristin K Howell2, Lara E Dozier1

  • 1Section of Neurobiology, Division of Biological Sciences, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0347, United States.

Molecular and Cellular Neurosciences
|December 9, 2017
PubMed
Summary

Cocaine addiction involves brain changes regulated by the Rpt6 protein. Phosphorylating Rpt6 at ser120 is crucial for cocaine-induced behavioral changes, suggesting a new therapeutic target.

Keywords:
26S proteasomeCocaineNucleus accumbensSensitizationUbiquitin

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Addiction Research

Background:

  • Repeated cocaine exposure induces synaptic modifications, leading to behavioral sensitization.
  • The ubiquitin proteasome system is vital for synaptic remodeling and implicated in addiction.
  • Rpt6 (26S proteasome ATPase subunit) phosphorylation at ser120 by CaMKIIα may regulate proteasome function.

Purpose of the Study:

  • To investigate the role of Rpt6 phosphorylation at ser120 in cocaine-induced locomotor sensitization.
  • To determine if cocaine affects proteasome activity and Rpt6 S120 phosphorylation in neuronal and brain tissues.

Main Methods:

  • Utilized wild-type and Rpt6 phospho-mimetic (ser120Asp) mice.
  • Administered cocaine to assess locomotor activity and sensitization.
  • Measured proteasome activity and Rpt6 S120 phosphorylation in cultured neurons and brain regions (nucleus accumbens, prefrontal cortex).

Main Results:

  • Cocaine increased proteasome activity and Rpt6 S120 phosphorylation in wild-type mice.
  • Cocaine failed to increase proteasome activity in Rpt6 ser120Asp mice.
  • Rpt6 ser120Asp mice exhibited a complete absence of cocaine-induced locomotor sensitization.

Conclusions:

  • Rpt6 phosphorylation at ser120 is critical for cocaine-induced locomotor sensitization.
  • Rpt6 phosphorylation regulates proteasome function in response to cocaine.
  • Targeting Rpt6 phosphorylation may offer a novel strategy for treating cocaine addiction and related behavioral plasticity.