Cerebrovascular Injury After Serial Exposure to Chronic Stress and Abstinence from Methamphetamine Self-Administration
| Autor: | Carmen M. Mitchell, Reka Natarajan, Nicole Harless, Bryan K. Yamamoto |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male media_common.quotation_subject lcsh:Medicine Self Administration Pharmacology Occludin Article Methamphetamine Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Animals Humans Chronic stress lcsh:Science media_common Cerebral Cortex Multidisciplinary Cyclooxygenase 2 Inhibitors business.industry lcsh:R Meth Abstinence medicine.disease Rats Substance abuse Cerebrovascular Disorders Disease Models Animal 030104 developmental biology chemistry Cyclooxygenase 2 Cerebrovascular Circulation Central Nervous System Stimulants lcsh:Q Self-administration business 030217 neurology & neurosurgery Stress Psychological Nimesulide medicine.drug |
| Zdroj: | Scientific Reports, Vol 8, Iss 1, Pp 1-10 (2018) Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-018-28970-1 |
| Popis: | Cerebrovascular damage caused by either exposure to stress or the widely abused drug, methamphetamine (Meth) is known but stress and drug abuse frequently occur in tandem that may impact their individual cerebrovascular effects. This study examined their co-morbid cerebrovascular effects during abstinence from self-administered Meth after the exposure to chronic unpredictable stress (CUS). Exposure to CUS prior to unrestricted Meth self-administration had no effect on Meth intake in rats; however, the pro-inflammatory mediator cyclooxygenase-2 (COX-2) and the breakdown of cell-matrix adhesion protein β-dystroglycan in isolated cerebral cortical capillaries were increased after 3 days of abstinence and persisted for 7 days. These changes preceded decreases in occludin, a key structural protein component of the blood-brain barrier. The decrease in occludin was blocked by the COX-2 specific inhibitor nimesulide treatment during abstinence from Meth. The changes in COX-2, β-dystroglycan, and occludin were only evident following the serial exposure to stress and Meth but not after either one alone. These results suggest that stress and voluntary Meth intake can synergize and disrupt cerebrovasculature in a time-dependent manner during abstinence from chronic stress and Meth. Furthermore, COX-2 inhibition may be a viable pharmacological intervention to block vascular changes after Meth exposure. |
| Databáze: | OpenAIRE |
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