Gender differences in cocaine-induced hyperactivity and dopamine transporter trafficking to the plasma membrane

Jing Deng, Xirong Zheng, Linyue Shang, Chang Guo Zhan, Fang Zheng

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


As well known, cocaine induces stimulant effects and dopamine transporter (DAT) trafficking to the plasma membrane of dopaminergic neurons. In the present study, we examined cocaine-induced hyperactivity along with cocaine-induced DAT trafficking and the recovery rate of the dopaminergic system in female rats in comparison with male rats, demonstrating interesting gender differences. Female rats are initially more sensitive to cocaine than male rats in terms of both the DAT trafficking and hyperactivity induced by cocaine. Particularly, intraperitoneal (i.p.) administration of 5 mg/kg cocaine induced significant hyperactivity and DAT trafficking in female rats but not in male rats. After repeated cocaine exposures (i.e., i.p. administration of 20 mg/kg cocaine every other day from Day 0 to Day 32), cocaine-induced hyperactivity in female rats gradually became a clear pattern of two phases, with the first phase of the hyperactivity lasting for only a few minutes and the second phase lasting for over an hour beginning at ~30 min, which is clearly different from that of male rats. It has also been demonstrated that the striatal DAT distribution of female rats may recover faster than that of male rats after multiple cocaine exposures. Nevertheless, despite the remarkable gender differences, our recently developed long-acting cocaine hydrolase, known as CocH5-Fc(M6), can similarly and effectively block cocaine-induced DAT trafficking and hyperactivity in both male and female rats.

Original languageEnglish
Article numbere13236
JournalAddiction Biology
Issue number6
StatePublished - Nov 2022

Bibliographical note

Funding Information:
This work was supported by the National Institutes of Health (NIH grants U01 DA051079, R01 DA056646, U18 DA052319, UH2/UH3 DA041115, R01 DA035552, R01 DA032910 and R01 DA013930).

Publisher Copyright:
© 2022 Society for the Study of Addiction.


  • cocaine addiction
  • cocaine hydrolysis
  • enzyme therapy

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology
  • Psychiatry and Mental health


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