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

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Lucía Améndola ◽  
Anna Ratuski ◽  
Daniel M. Weary
Keyword(s):  
Carbon Dioxide ◽  
Individual Differences ◽  
Control Treatment ◽  
Loss Of Consciousness ◽  
Sprague Dawley ◽  
Laboratory Rats ◽  
Avoidance Testing ◽  
Healthy Humans ◽  
Sprague Dawley Rats ◽  
Approach Avoidance

AbstractCarbon 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.

scholarly journals Individual differences in rat sensitivity to CO2

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0245347
Author(s):  
Lucía Améndola ◽  
Anna Ratuski ◽  
Daniel M. Weary
Keyword(s):  
Carbon Dioxide ◽  
Individual Differences ◽  
Sprague Dawley ◽  
Prevention Focus ◽  
Promotion Focus ◽  
Sprague Dawley Rats ◽  
Approach Avoidance ◽  
The Stability ◽  
Reward Motivation ◽  
Sweet Reward

Feelings of fear, anxiety, dyspnea and panic when inhaling carbon dioxide (CO2) are variable among humans, in part due to differences in CO2 sensitivity. Rat aversion to CO2 consistently varies between individuals; this variation in aversion may reflect CO2 sensitivity, but other personality traits could also account for individual differences in aversion. The aims of this study were to 1) assess the stability of individual differences in rat aversion to CO2, 2) determine if individual differences in sweet reward motivation are associated with variation in aversion to CO2, and 3) assess whether variation in aversion to CO2 is related to individual differences in motivation to approach gains (promotion focus) or maintain safety (prevention focus). Twelve female Sprague Dawley rats were exposed multiple times at three different ages (3, 9 and 16 months old) to CO2 in approach-avoidance testing to assess motivation to avoid CO2 against motivation to gain sweet rewards. Rats were also tested for motivation to find hidden sweet rewards, and for their motivation to approach rewards or darkness. Tolerance to CO2 increased with repeated exposures and was higher at older ages. Individual differences in aversion to CO2 were highly repeatable but unrelated to motivation for sweet rewards or the strength of promotion and prevention focus. These results indicate that individual differences in aversion to CO2 reflect variation in CO2 sensitivity.

scholarly journals Assessment of carbon dioxide, carbon dioxide/oxygen, isoflurane and pentobarbital killing methods in rats

2016 ◽  
Author(s):  
Jessica M Chisholm ◽  
Daniel SJ Pang
Keyword(s):  
Carbon Dioxide ◽  
Heart Rate ◽  
Loss Of Consciousness ◽  
Sprague Dawley ◽  
Loss Of Righting Reflex ◽  
Sprague Dawley Rats ◽  
General Order ◽  
Righting Reflex ◽  
High Concentrations ◽  
The Relationship

AbstractBackground:Exposure to carbon dioxide (CO2) gas as a killing method is aversive and exposure to high concentrations likely to be painful. Bradycardia during exposure to CO2 is associated with nociception and pain. However, it is unclear if bradycardia occurs before loss of consciousness as this is variably defined in the literature. The objectives of this study were to explore the relationship between recumbency, loss of righting reflex (LORR) and a quiescent electromyograph as measures of loss of consciousness, and identify the onset of bradycardia in relation to these measures.Methods:Thirty-two adult, female Sprague-Dawley rats were instrumented with a telemetry device and randomly assigned to one of four killing methods (100% CO2, CO2 (70%)/O2 (30%), isoflurane (5%) and intraperitoneal pentobarbital (200 mg/kg). Time to achieve recumbency, LORR, quiescent electromyograph, isoelectric electrocorticograph, heart rate and apnea were recorded.Results:The general order of progression was recumbency, LORR, quiescent electromyograph, isoelectric electrocorticograph and apnea. Recumbency preceded LORR in the majority of animals (CO2; 7/8, CO2/O2; 8/8, isoflurane; 5/8, pentobarbital; 4/8). Bradycardia occurred before recumbency in the CO2 (p = 0.0002) and CO2/O2 (p = 0.005) groups, with a 50% reduction in heart rate compared to baseline. The slowest (time to apnea) and least consistent killing methods were CO2/O2 (1180 ± 658.1s) and pentobarbital (875 [239 to 4680]s).Conclusion:Bradycardia, and consequently nociception and pain, occurs before loss of consciousness during CO2 exposure. Pentobarbital displayed an unexpected lack of consistency, questioning its classification as an acceptable euthanasia method in rats.

scholarly journals Cardiovascular and Metabolic Responses to Carbon Dioxide Euthanasia in Conscious and Anesthetized Rats

2020 ◽  
Vol 59 (6) ◽  
pp. 742-749 ◽  
Author(s):  
Kathryn E Nichols ◽  
Kimberly L Holliday-White ◽  
Heather M Bogie ◽  
Kim M Swearingen ◽  
Megan S Fine ◽  
...  
Keyword(s):  
Carbon Dioxide ◽  
Metabolic Responses ◽  
Loss Of Consciousness ◽  
Small Drop ◽  
Sprague Dawley ◽  
Glucose Levels ◽  
Chamber Volume ◽  
Sprague Dawley Rats ◽  
Physiologic Responses ◽  
Conscious Animals

Euthanasia is a necessary component in research and must be conducted humanely. Currently, regulated CO2 exposure in conscious rats is acceptable, but data are divided on whether CO2 alone is more distressing than anesthesia prior to CO2. To evaluate distress in rats, we compared physiologic responses to CO2 euthanasia with and without isoflurane preanesthesia. Male Sprague–Dawley rats were implanted with telemetry devices to measure mean arterial pressure (MAP), heart rate (HR), and blood glucose. Animals recovered for 2 wk and were then exposed to either 5% isoflurane (n = 6) or 100% CO2 (n = 7; calculated 30% chamber volume/min displacement) in their home cages to induce loss of consciousness. Euthanasia was then completed with CO2 in both groups. MAP and HR increased when the gas delivery lids were placed on the home cages of both groups. Both MAP and HR gradually decreased with isoflurane exposure. MAP increased and HR decreased with CO2 exposure. Glucose levels remained stable throughout the procedure, except for a small drop in conscious animals initially exposed to 100% CO2. These data suggest that both gases affect the measured parameters in a similar manner, and that environmental factors, such as gas delivery lid placement, also change these measurements.

scholarly journals Aversion to Desflurane and Isoflurane in Sprague-Dawley Rats (Rattus norvegicus)

Animals ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 950 ◽  
Author(s):  
Katrina Frost ◽  
Maaria Shah ◽  
Vivian S.Y. Leung ◽  
Daniel S.J. Pang
Keyword(s):  
Carbon Dioxide ◽  
Exposure Time ◽  
Washout Period ◽  
Rattus Norvegicus ◽  
Sprague Dawley ◽  
Initial Exposure ◽  
Treatment Groups ◽  
Avoidance Paradigm ◽  
Sprague Dawley Rats

Carbon dioxide and isoflurane are widely used for killing rats, yet may not truly achieve “euthanasia”, because they elicit aversion. The inhalant anesthetic desflurane is faster acting than isoflurane, representing a potential refinement. Using an aversion-avoidance paradigm, 24 rats were exposed to isoflurane or desflurane (n = 12 per group) at initial exposure. Fourteen rats were then re-exposed to isoflurane or desflurane (n = 7 per group), after a 7 days washout period. Initial exposure: time to recumbency was faster for desflurane than isoflurane (p = 0.0008, 95% CI [-12.9 to 32.6 s]), with 9/12 and 6/12 rats becoming recumbent, respectively. At initial exposure, there was no difference between groups in time to withdrawal (p = 0.714). At re-exposure, all rats withdrew and no rats became recumbent. Time to withdrawal at re-exposure did not differ between treatment groups (p = 0.083). Compared to initial exposure, time to withdrawal during re-exposure was similar for isoflurane (p = 0.228) and faster with desflurane (p = 0.012, 95% CI [19.1 to 49.5 s]). Isoflurane and desflurane are similarly aversive, with aversion increasing at re-exposure. The shorter time from exposure to recumbency with desflurane indicates that any distress is of a shorter duration when compared with isoflurane.

scholarly journals The cardiovascular and endocrine responses to voluntary and forced diving in trained and untrained rats

2010 ◽  
Vol 298 (1) ◽  
pp. R224-R234 ◽  
Author(s):  
Paul F. McCulloch ◽  
Karyn. M. DiNovo ◽  
Tiffanny M. Connolly
Keyword(s):  
Heart Rate ◽  
Sympathetic Activity ◽  
Peripheral Resistance ◽  
Cardiovascular Responses ◽  
Conscious Awareness ◽  
Sprague Dawley ◽  
Diving Response ◽  
Laboratory Rats ◽  
Cardiorespiratory Response ◽  
Sprague Dawley Rats

The mammalian diving response, consisting of apnea, bradycardia, and increased total peripheral resistance, can be modified by conscious awareness, fear, and anticipation. We wondered whether swim and dive training in rats would 1) affect the magnitude of the cardiovascular responses during voluntary and forced diving, and 2) whether this training would reduce or eliminate any stress due to diving. Results indicate Sprague-Dawley rats have a substantial diving response. Immediately upon submersion, heart rate (HR) decreased by 78%, from 453 ± 12 to 101 ± 8 beats per minute (bpm), and mean arterial pressure (MAP) decreased 25%, from 143 ± 1 to 107 ± 5 mmHg. Approximately 4.5 s after submergence, MAP had increased to a maximum 174 ± 3 mmHg. Blood corticosterone levels indicate trained rats find diving no more stressful than being held by a human, while untrained rats find swimming and diving very stressful. Forced diving is stressful to both trained and untrained rats. The magnitude of bradycardia was similar during both voluntary and forced diving, while the increase in MAP was greater during forced diving. The diving response of laboratory rats, therefore, appears to be dissimilar from that of other animals, as most birds and mammals show intensification of diving bradycardia during forced diving compared with voluntary diving. Rats may exhibit an accentuated antagonism between the parasympathetic and sympathetic branches of the autonomic nervous system, such that in the autonomic control of HR, parasympathetic activity overpowers sympathetic activity. Additionally, laboratory rats may lack the ability to modify the degree of parasympathetic outflow to the heart during an intense cardiorespiratory response (i.e., the diving response).

The incidence of chronic progressive nephrosis in young Sprague-Dawley rats from two different breeders

1998 ◽  
Vol 32 (4) ◽  
pp. 477-482 ◽  
Author(s):  
Maud Palm
Keyword(s):  
Kidney Function ◽  
Young Female ◽  
Female Rats ◽  
Common Finding ◽  
Sprague Dawley ◽  
Laboratory Rats ◽  
Toxicity Studies ◽  
Sprague Dawley Rats ◽  
Males And Females

Chronic progressive nephrosis (CPN) in rats may not only become a problem in long-term toxicity studies but also in short-term studies, if the breeding stock is not carefully selected with respect to the kidney function. This paper presents differences in kidney function between young rats of the same strain, Sprague-Dawley, but from two different breeders ('set A' and 'set B' rats). In set A rats, protein in the urine was present in the males, which is a common finding. In set B rats, not only the males but also the females excreted protein in the urine. The method used to detect protein in the urine does not normally show a positive protein result in the young female rats. At the age of 3 months signs of chronic progressive nephrosis were observed in 55% of the males and in 15% of the females in set B. Two months later, the incidence had increased to about 70–80% in males and 50% in females. At 8 months, the incidence was similar, but the severity had increased. These values were compared with those obtained from the set A rats, none of which showed any signs of the disease at the age of 5 months and only 5% of the males and females at the age of 8 months. The results indicated that an increased excretion of protein in the urine may be used as an indicator for chronic progressive nephrosis in the rat and that not only the strain but also the source is important in selecting laboratory rats for toxicity studies.

scholarly journals Differential Effects of Buffered Hypercapnia versus  Hypercapnic Acidosis on Shock and Lung Injury Induced by Systemic Sepsis

2009 ◽  
Vol 111 (6) ◽  
pp. 1317-1326 ◽  
Author(s):  
Brendan D. Higgins ◽  
Joseph Costello ◽  
Maya Contreras ◽  
Patrick Hassett ◽  
Daniel O' Toole ◽  
...  
Keyword(s):  
Carbon Dioxide ◽  
Lung Injury ◽  
Cecal Ligation ◽  
Hypercapnic Acidosis ◽  
Cecal Ligation And Puncture ◽  
Sprague Dawley ◽  
Systemic Sepsis ◽  
Sprague Dawley Rats ◽  
Hemodynamic Deterioration ◽  
Hemodynamic Profile

Background Acute hypercapnic acidosis protects against lung injury caused by nonseptic insults and after both pulmonary and systemic sepsis. The authors wished to dissect the contribution of the acidosis versus hypercapnia per se to the effects of hypercapnic acidosis on the hemodynamic profile and severity of lung injury induced by systemic sepsis. Methods In the hypercapnic acidosis series, adult male Sprague-Dawley rats were randomized to normocapnia or hypercapnic acidosis-produced by adding 5% carbon dioxide to the inspired gas-and cecal ligation and puncture performed. In the buffered hypercapnia series, animals were first randomized to housing under conditions of environmental normocapnia or hypercapnia-produced by exposure to 8% carbon dioxide-to allow renal buffering. After 96 h, cecal ligation and puncture was performed. In both series, the animals were ventilated for 6 h, and the severity of the lung injury and hemodynamic deterioration were assessed. Results Both hypercapnic acidosis and buffered hypercapnia attenuated the development and severity of hypotension and reduced lactate accumulation compared to normocapnia. Hypercapnic acidosis reduced lung injury and inflammation, decreased mean (+ or - SD) bronchoalveolar lavage protein concentration (232 + or - 50 versus 279 + or - 27 microg x ml(-1)) and median neutrophil counts (3,370 versus 9,120 cells x ml(-1)), and reduced histologic lung injury. In contrast, buffered hypercapnia did not reduce the severity of systemic sepsis induced lung injury. Conclusions Both hypercapnic acidosis and buffered hypercapnia attenuate the hemodynamic consequences of systemic sepsis. In contrast, hypercapnic acidosis, but not buffered hypercapnia, reduced the severity of sepsis-induced lung injury.

scholarly journals Strain differences in purified rat hepatic 3 α-hydroxysteroid UDP-glucuronosyltransferase

1985 ◽  
Vol 230 (2) ◽  
pp. 403-409 ◽  
Author(s):  
M D Green ◽  
C N Falany ◽  
R B Kirkpatrick ◽  
T R Tephly
Keyword(s):  
Individual Differences ◽  
Chenodeoxycholic Acid ◽  
Wistar Rats ◽  
Glucuronic Acid ◽  
Strain Differences ◽  
Sprague Dawley ◽  
Qualitative And Quantitative ◽  
Sprague Dawley Rats ◽  
Different Populations ◽  
Udp Glucuronosyltransferase

Qualitative and quantitative differences of purified hepatic 3 α-hydroxysteroid UDP-glucuronosyltransferase were investigated in Wistar and Sprague-Dawley rats. Individual differences in the glucuronidation rate of androsterone and chenodeoxycholic acid were observed in hepatic microsomal fractions from Wistar but not Sprague-Dawley rats. No individual variation was observed in the glucuronidation of testosterone, p-nitrophenol or oestrone. The 3 α-hydroxysteroid UDP-glucuronosyltransferases from livers of Wistar and Sprague-Dawley rats were isolated and highly purified by using Chromatofocusing and affinity chromatography. The amount of 3 α-hydroxysteroid UDP-glucuronosyltransferase in the liver of Wistar rats exhibiting low rates for androsterone glucuronidation is about 10% or less than that found in hepatic microsomal fractions obtained from Wistar rats having high rates for androsterone glucuronidation. The apparent Km for androsterone with purified 3 α-hydroxysteroid UDP-glucuronosyltransferase from Wistar rats with high glucuronidation activity (6 microM) was not different from that observed for the enzyme purified from Sprague-Dawley animals, whereas that for the enzyme purified from Wistar rats with low glucuronidation activity was substantially higher (120 microM). Despite the differences in apparent Km values for androsterone, the apparent Km for UDP-glucuronic acid (0.3 mM) was not different in the different populations of rats.

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