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Variation in the onset of CO₂-induced anxiety in female Sprague Dawley rats.

ABSTRACT: Carbon dioxide (CO₂) is commonly used to kill laboratory rats. Rats find CO₂ aversive and aversion varies between individuals, indicating that rats vary in CO₂ sensitivity. Healthy humans experience feelings of anxiety at concentrations similar to those avoided by rats, and these feelings are diminished by the administration of benzodiazepines. Our aim was to assess the effects of the benzodiazepine midazolam on individual thresholds of rat aversion to CO₂. Six female Sprague Dawley rats were repeatedly exposed to CO₂ gradual-fill in approach-avoidance testing. The first three exposures were to a control-treatment followed by three exposures to midazolam (0.375?mg/kg). Within each treatment aversion to CO₂ was not affected by exposure number; however, tolerance increased from an average of 10.7% CO₂ avoided during control sessions, to 15.5% CO₂ avoided when treated with midazolam. These results indicate that rats experience anxiety when exposed to CO₂, and that variation in rat CO₂ sensitivity is driven by individual differences in the onset of these feelings of anxiety. No rat tolerated CO₂ concentrations required to induce loss of consciousness.

SUBMITTER: Amendola L

PROVIDER: S-EPMC6908729 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Variation in the onset of CO2-induced anxiety in female Sprague Dawley rats.

Améndola Lucía L Ratuski Anna A Weary Daniel M DM

Scientific reports 20191212 1

Carbon dioxide (CO2) is commonly used to kill laboratory rats. Rats find CO2 aversive and aversion varies between individuals, indicating that rats vary in CO2 sensitivity. Healthy humans experience feelings of anxiety at concentrations similar to those avoided by rats, and these feelings are diminished by the administration of benzodiazepines. Our aim was to assess the effects of the benzodiazepine midazolam on individual thresholds of rat aversion to CO2</ ...[more]

PMID: 31831816

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Project description:Polychlorinated biphenyls (PCBs) are organic chemicals that were traditionally produced and widely used in industry as mixtures and are presently formed as byproducts of pigment and dye manufacturing. They are known to persist and bioaccumulate in the environment. Some have been shown to induce liver cancer in rodents. Although the mechanism of the toxicity of PCBs is unknown, it has been shown that they increase oxidative stress, including lipid peroxidation. We hypothesized that oxidative stress-induced DNA damage could be a contributor for PCB carcinogenesis and analyzed several DNA adducts in female Sprague-Dawley rats exposed to 3,3',4,4',5-pentachlorobiphenyl (PCB 126), 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153), and a binary mixture (PCB 126 + 153) for 14, 31, and 53 wks. Eight adducts were measured to profile oxidative DNA lesions, including 8-oxo-deoxyguanosine (8-oxo-dG), 1,N(6)-ethenodeoxyadenosine (1,N(6)-εdA), N(2),3-ethenoguanine (N(2),3-εG), 1,N(2)-ethenodeoxyguanosine (1,N(2)-εdG), as well as malondialdehyde (M1dG), acrolein (AcrdG), crotonaldehyde (CrdG), and 4-hydroxynonenal-derived dG adducts (HNEdG) by LC-MS/MS analysis. Statistically significant increases were observed for 8-oxo-dG and 1,N(6)-εdA concentrations in hepatic DNA of female rats exposed to the binary mixture (1000 ng/kg/day + 1000 μg/kg/day) but not in rats exposed to PCB 126 (1000 ng/kg/day) or PCB 153 (1000 μg/kg/day) for 14 and 31 wks. However, exposure to PCB 126 (1000 ng/kg/day) for 53 wks significantly increased 8-oxo-dG, 1,N(6)-εdA, AcrdG, and M1dG. Exposure to PCB 153 (1000 μg/kg/day) for 53 wks increased 8-oxo-dG, and 1,N(6)-εdA. Exposure to the binary mixture for 53 wks increased 8-oxo-dG, 1,N(6)-εdA, AcrdG, 1,N(2)-εdG, and N(2),3-εG significantly above control groups. Increased hepatic oxidative DNA adducts following exposure to PCB 126, PCB 153, or the binary mixture shows that an increase in DNA damage may play an important role in hepatic toxicity and carcinogenesis in female Sprague-Dawley rats.

Dataset Information

Variation in the onset of CO₂-induced anxiety in female Sprague Dawley rats.

Publications

Variation in the onset of CO<sub>2</sub>-induced anxiety in female Sprague Dawley rats.

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