Chronic cocaine administration upregulates FKBP5 in the extended amygdala of male and female rats

Drug Alcohol Depend. 2019 Jun 1;199:101-105. doi: 10.1016/j.drugalcdep.2019.02.019. Epub 2019 Apr 18.


Background: Dysregulation of glucocorticoid receptors has been implicated in addiction and stress-related disorders. FKBP5 is a co-chaperone of the glucocorticoid receptor and regulates receptor sensitivity. While FKBP5 is known to be involved in mood- and stress-related disorders, less is known regarding FKBP5 and cocaine abuse. This study investigated the regulation of FKBP5 expression in the extended amygdala and paraventricular nucleus of the hypothalamus, regions important in the control of stress-responses and HPA axis function, following chronic and acute cocaine administration.

Methods: Adult male and female rats received saline or cocaine three times per day for 1 or 14 days. Brain tissue was collected 30 min, 24 h, 48 h, 7 days or 14 days following the final injection. FKBP5 mRNA was measured by qRT-PCR in the central nucleus of the amygdala (CeA), bed nucleus of the stria terminalis (BNST) and paraventricular nucleus (PVN).

Results: FKBP5 mRNA levels were significantly elevated as a result of chronic cocaine administration in both males and females in the PVN and BNST 30 min and 24 h after the final injection. In females, FKBP5 was also elevated in the CeA. Following acute cocaine, FKBP5 gene expression was unaltered except for elevated levels in the BNST of females 24 h later.

Conclusions: These results demonstrate that FKBP5 mRNA is regulated by cocaine administration. Increased FKBP5 expression may play a role in the dysregulation of the stress axis following chronic cocaine exposure, contributing to the negative affective symptoms of cocaine withdrawal.

Keywords: Anxiety; Depression; FKBP51; HPA axis; Sex differences; Stress.

Publication types

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

MeSH terms

  • Amygdala / drug effects*
  • Amygdala / metabolism*
  • Animals
  • Cocaine / administration & dosage*
  • Cocaine-Related Disorders / metabolism
  • Female
  • Hypothalamo-Hypophyseal System / drug effects
  • Hypothalamo-Hypophyseal System / metabolism
  • Male
  • Pituitary-Adrenal System / drug effects
  • Pituitary-Adrenal System / metabolism
  • Rats
  • Septal Nuclei / drug effects
  • Septal Nuclei / metabolism
  • Tacrolimus Binding Proteins / biosynthesis*
  • Up-Regulation / drug effects*
  • Up-Regulation / physiology


  • Tacrolimus Binding Proteins
  • tacrolimus binding protein 5
  • Cocaine