Impact of Stress Hormone on Brain Damage and Inflammatory Responses Resulting from Methamphetamine Exposure in Rats

Details

• Personal Author:
  Michalovicz, Lindsay T. ; Billig, Brenda K. ; Felton, Christopher M. ; Yilmaz, Ali A. ; Kelly, K. A.
• Description:
  Background and Purpose: Over the last several years, illicit drug use has increased in the U.S. including drugs like methamphetamine. As a dopaminergic neurotoxicant, methamphetamine exposure poses risk of injury to dopaminergic neurons, brain inflammation, and mortality. While illicit drug use constitutes an obvious health risk to the user, public safety personnel including law enforcement, emergency medical service, and corrections officers, are at risk for unintentional exposure to these drugs when interacting with contaminated materials or individuals under the influence. While unintentional exposure is likely to be at a lower drug concentration, a health risk may exist particularly when considering other work environment conditions. Work-related stress is a major concern for public safety personnel due to the high risk of exposure to repeated high-stress incidents, as well as work organizational stress factors. In previous studies, subchronic exposure to stress hormone was shown to exacerbate the neuroinflammatory and neural injury responses to several neurotoxicants in rodent models. The aim of the current study was to identify low doses of methamphetamine that did not produce neuroinflammation or neural damage on their own and evaluate the ability for prior stress hormone exposure to modulate these responses in a rat model of exposure. Methods: Adult male Sprague-Dawley rats were given corticosterone (200 mg/L in 0.6% ethanol) in their drinking water for 7 days followed by a single subcutaneous injection of methamphetamine (5, 7.5, or 10 mg/kg). Body temperature was measured at 1 and 2 hours post-methamphetamine exposure. Markers for neuroinflammation and dopaminergic neuron damage were assessed in the striatum, hippocampus, and cortex. Inflammatory cytokine mRNA was measured in the brain by qRT-PCR. Glial fibrillary acidic protein (GFAP), a marker of astrogliosis, and tyrosine hydroxylase (TH), a marker for dopaminergic neurons, proteins were measured by ELISA. Results: Exposure to corticosterone significantly modulated the body temperature response to methamphetamine exposure; all doses tested showed a significant temperature elevation compared to corticosterone alone while only the 10 mg/kg, s.c. methamphetamine dose resulted in significant hyperthermia on its own. Neuroinflammatory changes were observed as early as 12 hrs post- methamphetamine. In the striatum, which is the site of dopaminergic nerve terminals from the substantia nigra and methamphetamine -induced damage, the 10 mg/kg, s.c. dose of methamphetamine significantly increased several cytokines regardless of corticosterone exposure status. However, the 7.5 mg/kg, s.c. dose significantly increased inflammatory cytokine mRNA expression only with prior corticosterone exposure. Interestingly, while methamphetamine typically targets the dopaminergic nerve terminals of the striatum, prior exposure to stress hormone expanded the neuroinflammatory effects of methamphetamine to the hippocampus and cortex. Conclusions: Stress is a common workplace environmental factor and the nature of public safety work constitutes a high work-related stress environment due to exposure to traumatic events, as well as work organizational factors. Here, prior stress hormone exposure, a surrogate for stressors, was demonstrated to modulate the response to low dose methamphetamine exposure increasing its negative effects on the brain. These data also highlight the correlation between methamphetamine- induced hyperthermia and detrimental effects on the brain, with prior stress increasing the risk of hyperthermia with lower dosages of methamphetamine. Overall, these findings suggest that the chronic stress experienced by public safety personnel may pose a greater risk for adverse neurological health outcomes resulting from unintentional exposure to methamphetamine. Considering the association between dopaminergic neuron loss and long-term neurological disease, such as Parkinson's Disease, further work is needed to assess the potential long-term consequences of these combined exposures. Description provided by NIOSH
• Subjects:
  • Immune System
  • Methamphetamine
  • Occupational Exposure
  • Occupational Health
  • Safety
  • Stress, Psychological
• Keywords:
  • Drugs; Occupational exposure; Methamphetamine; Job stress; Hormone activity; Neurotoxicology; Immune reaction; Brain damage
• Source:
  Toxicologist 2025 Mar; 204(S1):617-618
• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Philadelphia Region OSHA ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  3 pdf pages
• Volume:
  204
• NIOSHTIC Number:
  nn:20071591
• CAS Registry Number:
  • Methamphetamine (CAS RN 537-46-2)
• Federal Fiscal Year:
  2025
• NORA Priority Area:
  Public Safety
• Peer Reviewed:
  False
• Download URL:
  https://stacks.cdc.gov/view/cdc/259366/cdc_259366_DS1.pdf
• File Type:
  [PDF - 298.18 KB]
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:d7ee259bdd4b2bceb2304c37d69d8d7d048217d047a126b46f5e700d995c07aa17cc0fefd2550795df9990daa854adf9b9b812ab0d2d94a563e52070f9fb53db