JQ1 attenuates psychostimulant- but not opioid-induced conditioned place preference

Behav Brain Res. 2022 Feb 10:418:113644. doi: 10.1016/j.bbr.2021.113644. Epub 2021 Oct 28.

Abstract

Epigenetic mechanisms play important roles in the neurobiology of substance use disorder. In particular, bromodomain and extra-terminal domain (BET) proteins, a class of histone acetylation readers, have been found to regulate cocaine conditioned behaviors, but their role in the behavioral response to other drugs of abuse remains unclear. To address this knowledge gap, we examined the effects of the BET inhibitor, JQ1, on nicotine, amphetamine, morphine, and oxycodone conditioned place preference (CPP). Similar to previous cocaine studies, systemic administration of JQ1 caused a dose-dependent reduction in the acquisition of amphetamine and nicotine CPP in male mice. However, in opioid studies, JQ1 did not alter morphine or oxycodone CPP. Investigating the effects of JQ1 on other types of learning and memory, we found that JQ1 did not alter the acquisition of contextual fear conditioning. Together, these results indicate that BET proteins play an important role in the acquisition of psychostimulant-induced CPP but not the acquisition of opioid-induced CPP nor contextual fear conditioning.

Keywords: Amphetamine; BET; Bromodomain; Epigenetics; JQ1; Morphine; Nicotine; Oxycodone.

Publication types

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

MeSH terms

  • Amphetamine / pharmacology
  • Anesthetics, Local / pharmacology*
  • Animals
  • Azepines / administration & dosage*
  • Behavior, Animal / drug effects*
  • Central Nervous System Stimulants / pharmacology*
  • Cocaine / pharmacology
  • Conditioning, Psychological / drug effects*
  • Dose-Response Relationship, Drug*
  • Epigenomics
  • Learning / drug effects
  • Male
  • Memory / drug effects
  • Mice
  • Morphine / pharmacology
  • Nicotine / pharmacology
  • Triazoles / administration & dosage*

Substances

  • (+)-JQ1 compound
  • Anesthetics, Local
  • Azepines
  • Central Nervous System Stimulants
  • Triazoles
  • Nicotine
  • Morphine
  • Amphetamine
  • Cocaine