title: Tempol treatment reduces anxiety-like behaviors induced by multiple anxiogenic drugs in rats.
abstract: We have published that pharmacological induction of oxidative stress (OS) causes anxiety-like behavior in rats. Using animal models, we also have established that psychological stress induces OS and leads to anxiety-like behaviors. All evidence points towards the causal role of OS in anxiety-like behaviors. To fully ascertain the role of OS in anxiety-like behaviors, it is reasonable to test whether the pro-anxiety effects of anxiogenic drugs caffeine or N-methyl-beta-carboline-3-carboxamide (FG-7142) can be mitigated using agents that minimize OS. In this study, osmotic pumps were either filled with antioxidant tempol or saline. The pumps were attached to the catheter leading to the brain cannula and inserted into the subcutaneous pocket in the back pocket of the rat. Continuous i.c.v. infusion of saline or tempol in the lateral ventricle of the brain (4.3 mmol/day) was maintained for 1 week. Rats were intraperitoneally injected either with saline or an anxiogenic drug one at a time. Two hours later all groups were subjected to behavioral assessments. Anxiety-like behavior tests (open-field, light-dark and elevated plus maze) suggested that tempol prevented anxiogenic drug-induced anxiety-like behavior in rats. Furthermore, anxiogenic drug-induced increase in stress examined via plasma corticosterone and increased oxidative stress levels assessed via plasma 8-isoprostane were prevented with tempol treatment. Protein carbonylation assay also suggested preventive effect of tempol in the prefrontal cortex brain region of rats. Antioxidant protein expression and pro-inflammatory cytokine levels indicate compromised antioxidant defense as well as an imbalance of inflammatory response.
authors: Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, 77204, United States of America.
authors: Gaurav
authors: G
authors: Patki
authors: Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, 77204, United States of America.
authors: Ankita
authors: A
authors: Salvi
authors: Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, 77204, United States of America.
authors: Hesong
authors: H
authors: Liu
authors: Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, 77204, United States of America.
authors: Fatin
authors: F
authors: Atrooz
authors: Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, 77204, United States of America.
authors: Isam
authors: I
authors: Alkadhi
authors: Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, 77204, United States of America.
authors: Matthew
authors: M
authors: Kelly
authors: Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, 77204, United States of America.
authors: Samina
authors: S
authors: Salim
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001007:Anxiety / Q000097:blood / Q000139:chemically induced* / Q000188:drug therapy*; D001522:Behavior, Animal / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D003497:Cyclic N-Oxides / Q000494:pharmacology / Q000627:therapeutic use*; D003624:Darkness; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007249:Inflammation / Q000473:pathology; D007260:Infusion Pumps; D008297:Male; D018782:Maze Learning; D018384:Oxidative Stress / Q000187:drug effects; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D020710:RGS Proteins / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D013113:Spin Labels; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D015415:Biomarkers; D003497:Cyclic N-Oxides; D016760:Proto-Oncogene Proteins c-fos; D020710:RGS Proteins; C514563:RGS2 protein, rat; D013113:Spin Labels; D013482:Superoxide Dismutase; C001803:tempol; D003345:Corticosterone