Sex differences in activation of the hypothalamic–pituitary–adrenal axis by methamphetamine
Version of Record online: 10 FEB 2014
© 2014 International Society for Neurochemistry
Journal of Neurochemistry
Volume 129, Issue 3, pages 495–508, May 2014
How to Cite
J. Neurochem. (2014) 129, 495–508.
- Issue online: 19 APR 2014
- Version of Record online: 10 FEB 2014
- Accepted manuscript online: 9 JAN 2014 02:59AM EST
- Manuscript Accepted: 2 JAN 2014
- Manuscript Revised: 30 DEC 2013
- Manuscript Received: 22 NOV 2013
- NIDA. Grant Number: T32DA007262
- Oregon Health and Science University
- HPA axis, corticosterone;
- arginine vasopressin, glucocorticoid receptor;
- sex difference
Dysregulation of hypothalamic–pituitary–adrenal (HPA) axis activation is associated with changes in addiction-related behaviors. In this study, we tested whether sex differences in the acute effects of methamphetamine (MA) exposure involve differential activation of the HPA axis. Male and female mice were injected with MA (1 mg/kg) or saline for comparison of plasma corticosterone and analysis of the immediate early gene c-Fos in brain. There was a prolonged elevation in corticosterone levels in female compared to male mice. C-Fos was elevated in both sexes following MA in HPA axis-associated regions, including the hypothalamic paraventricular nucleus (PVN), central amygdala, cingulate, and CA3 hippocampal region. MA increased the number of c-Fos and c-Fos/glucocorticoid receptor (GR) dual-labeled cells to a greater extent in males than females in the cingulate and CA3 regions. MA also increased the number of c-fos/vasopressin dual-labeled cells in the PVN as well as the number and percentage of c-Fos/GR dual-labeled cells in the PVN and central amygdala, although no sex differences in dual labeling were found in these regions. Thus, sex differences in MA-induced plasma corticosterone levels and activation of distinct brain regions and proteins involved in HPA axis regulation may contribute to sex differences in acute effects of MA on the brain.
Methamphetamine induces a prolonged plasma corticosterone response in females compared to males. This may be mediated by increased neural activation, involving a greater activation of glucocorticoid receptor-positive cells, in males in the CA3 and cingulate brain regions, which are involved in negative feedback functions. These findings indicate a sex difference in the neural regulation of methamphetamine-induced plasma corticosterone release.