A functional eEF2K-eEF2 pathway in the NAc is critical for the expression of cocaine-induced psychomotor sensitisation and conditioned place preference

Tehila Beiser, Elvira Lisniansky, Moriya Weitz, Alexey Bingor, Etty Grad, Kobi Rosenblum, Claire Thornton, Rami Yaka

Research output: Contribution to journalArticlepeer-review

Abstract

Recent evidence links synaptic plasticity and mRNA translation, via the eukaryotic elongation factor 2 kinase (eEF2K) and its only known substrate, eEF2. However, the involvement of the eEF2 pathway in cocaine-induced neuroadaptations and cocaine-induced behaviours is not known. Knock-in (KI) mice and shRNA were used to globally and specifically reduce eEF2K expression. Cocaine psychomotor sensitization and conditioned place preference were used to evaluate behavioural outcome. Changes in eEF2 phosphorylation were determined by western blot analyses. No effect was observed on the AMPA/NMDA receptor current ratio in the ventral tegmental area, 24 h after cocaine injection in eEF2K-KI mice compared with WT. However, development and expression of cocaine psychomotor sensitization were decreased in KI mice. Phosphorylated eEF2 was decreased one day after psychomotor sensitization and returned to baseline at seven days in the nucleus accumbens (NAc) of WT mice, but not in eEF2K-KI mice. However, one day following cocaine challenge, phosphorylated eEF2 decreased in WT but not KI mice. Importantly, specific targeting of eEF2K expression by shRNA in the NAc decreased cocaine condition place preference. These results suggest that the eEF2 pathway play a role in cocaine-induced locomotor sensitization and conditioned place preference.

Original languageEnglish
Article number460
JournalTranslational Psychiatry
Volume12
Issue number1
DOIs
StatePublished - Dec 2022

Bibliographical note

Funding Information:
This work was supported by the Israeli Drug Authority (RY), The Israel Science Foundation (RY, #1283/16), IMRIC Hub for Addiction Research (RY), the David R. Bloom Center for Pharmacy at the Hebrew University of Jerusalem (RY) and by a Royal Society International Exchanges award (CT, RY, IES\R3\170125).

Publisher Copyright:
© 2022, The Author(s).

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Biological Psychiatry

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