title: Immediate and lasting effects of chronic daily methamphetamine exposure on activation of cells in hypothalamic-pituitary-adrenal axis-associated brain regions.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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 (Experiment 2) Compared to mice receiving their first dose of MA, mice chronically treated with MA, withdrawn, and re-administered MA, showed decreased c-Fos expressing cells within the central and basolateral amygdala, BNST, and CA3.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.
authors.affiliation: Department of Behavioral Neuroscience, Oregon Health and Science University Portland, Portland, OR, 97239, USA. dzuloaga@albany.edu.|Department of Psychology, University at Albany, Albany, NY, 12222, USA. dzuloaga@albany.edu.
authors.forename: Damian G
authors.initials: DG
authors.lastname: Zuloaga
authors.affiliation: Department of Behavioral Neuroscience, Oregon Health and Science University Portland, Portland, OR, 97239, USA.
authors.forename: Lance A
authors.initials: LA
authors.lastname: Johnson
authors.affiliation: Department of Behavioral Neuroscience, Oregon Health and Science University Portland, Portland, OR, 97239, USA.
authors.forename: Sydney
authors.initials: S
authors.lastname: Weber
authors.affiliation: Department of Behavioral Neuroscience, Oregon Health and Science University Portland, Portland, OR, 97239, USA.|Department of Neurology, Oregon Health and Science University Portland, Portland, OR, 97239, USA.|Department of Radiation Medicine, Oregon Health and Science University Portland, Portland, OR, 97239, USA.|Division of Neuroscience, ONPRC, Oregon Health and Science University Portland, Portland, OR, 97239, USA.
authors.forename: Jacob
authors.initials: J
authors.lastname: Raber
mesh_terms: D000679:Amygdala / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D056654:CA3 Region, Hippocampal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003345:Corticosterone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000166:cytology / Q000187:drug effects*; D007150:Immunohistochemistry; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects; D010913:Pituitary-Adrenal System / Q000166:cytology / Q000187:drug effects*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D012686:Septal Nuclei / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: D000697:Central Nervous System Stimulants; D016760:Proto-Oncogene Proteins c-fos; D008694:Methamphetamine; D003345:Corticosterone
keywords: Glucocorticoid; HPA Axis; Methamphetamine