Rationale: Chronic methamphetamine (MA) abuse leads to dependence and symptoms of withdrawal after use has ceased. Negative mood states associated with withdrawal, as well as drug reinstatement, have been linked to drug-induced disruption of the hypothalamic-pituitary-adrenal (HPA) axis. However, effects of chronic MA exposure or acute MA exposure following withdrawal on neural activation patterns within brain regions that regulate the HPA axis are unknown. Objectives: In this study, neural activation patterns were assessed by quantification of c-Fos protein in mice exposed to different regimens of MA administration. Methods: (Experiment 1) Adult male mice were treated with MA (5 mg/kg) or saline once or once daily for 10 days. (Experiment 2) Mice were treated with MA or saline once daily for 10 days and following a 10-day withdrawal period were re-administered a final dose of MA or saline. c-Fos was quantified in brains after the final injection. Results: (Experiment 1) Compared to exposure to a single dose of MA (5 mg/kg), chronic MA exposure decreased the number of c-Fos expressing cells in the paraventricular hypothalamus, dorsomedial hypothalamus, central amygdala, basolateral amygdala, bed nucleus of the stria terminalis (BNST), and CA3 hippocampal region. (Experiment 2) Compared to mice receiving their first dose of MA, mice chronically treated with MA, withdrawn, and re-administered MA, showed decreased c-Fos expressing cells within the central and basolateral amygdala, BNST, and CA3. Conclusions: HPA axis-associated amygdala, extended amygdala, and hippocampal regions endure lasting effects following chronic MA exposure and therefore may be linked to stress-related withdrawal symptoms.
|Number of pages||12|
|State||Published - Feb 1 2016|
Bibliographical noteFunding Information:
The authors acknowledge Tessa Marzulla, Tara Kugelman, and Chi Phan for their expert technical assistance. Funding was provided by NIDA T32DA007262, an Oregon Health and Science University Tartar Award, and the Oregon Health and Science University development account of Dr. Raber.
© 2015 Springer-Verlag Berlin Heidelberg.
- HPA Axis
ASJC Scopus subject areas