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Sex differences in activation of the hypothalamic–pituitary–adrenal axis by methamphetamine
Author(s) -
Zuloaga Damian G.,
Johnson Lance A.,
Agam Maayan,
Raber Jacob
Publication year - 2014
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.12651
Subject(s) - endocrinology , medicine , corticosterone , hypothalamic–pituitary–adrenal axis , glucocorticoid receptor , methamphetamine , glucocorticoid , amygdala , vasopressin , hippocampal formation , hypothalamus , immediate early gene , biology , chemistry , psychology , hormone , gene expression , gene , biochemistry
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 CA 3 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 CA 3 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.