Nalmefene reverses carfentanil-induced loss of righting reflex and respiratory depression in rats

2014 ◽  
Vol 738 ◽  
pp. 153-157 ◽  
Author(s):  
Zheng Yong ◽  
Xiang Gao ◽  
Wentao Ma ◽  
Huajing Dong ◽  
Zehui Gong ◽  
...  
Author(s):  
Meghan M. Louis ◽  
Gregory Scott ◽  
Dustin Smith ◽  
Brigid V. Troan ◽  
Larry J. Minter ◽  
...  

Euthanasia techniques in amphibians are poorly described and sparsely validated. This study investigated potassium chloride (KCl) for euthanasia of anesthetized marine toads ( Rhinella marina ). Twenty three toads were immersed in buffered MS-222 (2 g/L) for five minutes (min) beyond loss of righting reflex, manually removed, and randomly administered KCl (n = 6/group) via one of three routes: intracardiac at 10 mEq/kg (IC), intracoelomic at 100 mEq/kg (ICe), or immersion at 4500 mEq/L (IMS) or no treatment (C) (n = 5/group). Doppler sounds were assessed continuously from prior to treatment until two min post-treatment and every five min thereafter until sound cessation or resumption of spontaneous movement. Plasma potassium concentration (K+) was measured at the time of Doppler sound cessation in ICe and IMS. In IC, ICe, IMS, and C, Doppler sound cessation occurred in 4/6, 6/6, 6/6, and 1/5 toads with median (range) or mean + SD times of 0.23 (0-4.65), 17.5 + 9.0, 40.6 + 10.9, and >420 min, respectively. Nonsuccess in 2/6 toads in IC was suspected due to technique failure. Plasma K+ exceeded the limits of detection (>9 mmol/L) in 12/12 toads in ICe and IMS. Five of six toads in C resumed spontaneous movement at median (range) times of 327 (300-367) min. KCl delivered via an intracardiac, intracoelomic, or immersion routes resulted in Doppler sound cessation in 16 of 18 toads and may be appropriate for euthanasia of anesthetized marine toads.


2000 ◽  
Vol 93 (3) ◽  
pp. 837-843 ◽  
Author(s):  
Robert Dickinson ◽  
Ian White ◽  
William R. Lieb ◽  
Nicholas P. Franks

Background Although it is accepted widely that optically active intravenous general anesthetics produce stereoselective effects in animals, the situation regarding volatile agents is confused. Conventional studies with scarce isoflurane enantiomers have been limited to small numbers of animals and produced conflicting results. By injecting these volatile enantiomers intravenously, however, it is possible to study large numbers of animals and obtain reliable results that can help to identify the molecular targets for isoflurane. Methods Pure isoflurane enantiomers were administered intravenously to rats after solubilization in a lipid emulsion. The ability of each enantiomer to produce a loss of righting reflex was determined as a function of dose, and quantal dose-response curves were constructed. In addition, sleep times were recorded with each enantiomer. Chiral gas chromatography was used to measure relative enantiomer concentrations in the brains of rats injected with racemic isoflurane. Results The S(+)-enantiomer was 40 +/- 8% more potent than the R(-)-enantiomer at producing a loss of righting reflex. The S(+)-enantiomer induced longer sleep times (by about 50%) than did the R(-)-enantiomer. Rats anesthetized by a dose of racemic isoflurane sufficient to achieve a half-maximal effect had essentially identical brain concentrations of the two enantiomers. Conclusions The S(+)-enantiomer of the general anesthetic isoflurane is significantly (P < 0.001) more potent than the R(-)-enantiomer at causing a loss of righting reflex in rats. This confirms the view that isoflurane acts by binding to chiral sites. The observed degree of stereoselectivity provides a useful guide for ascertaining from in vitro experiments which molecular targets are most likely to play major roles in the loss of righting reflex caused by isoflurane.


2002 ◽  
Vol 97 (4) ◽  
pp. 906-911 ◽  
Author(s):  
Avery Tung ◽  
Martin J. Szafran ◽  
Bryan Bluhm ◽  
Wallace B. Mendelson

Background Sleep and anesthesia differ physiologically but produce a similar loss of responsiveness to environmental stimuli. Recent data suggest that neuronal networks active in naturally occurring sleep also play a role in the anesthetized state. Changes in the propensity to sleep may then modify the response to anesthetic agents. The authors tested the hypothesis that sleep-deprived rats would require less anesthetic than rested rats to achieve a similar loss of responsiveness. Methods Rats were subjected to a 24-h period of either sleep deprivation or ad libitum activity. Sleep deprivation was produced by placing rats on a disk that rotated when sleep was detected by electroencephalographic and electromyographic (EEG, EMG) monitoring. A fixed dose of anesthetic agent was then administered, and the time required to induce loss of righting reflex was measured. Anesthetic administration was then stopped, and the time to recovery measured. All rats received both treatments separated by 7 days. Results Sleep deprivation reduced the time to loss of righting reflex by 40% for propofol (P < 0.025) and 55% for isoflurane (P < 0.025) and prolonged the time to recovery. In a separate control experiment, exposure to the deprivation environment but with disk rotation modified to allow adequate sleep did not affect the response to anesthetic administration. Conclusions Sleep deprivation significantly potentiated the ability of inhaled and intravenous anesthetic agents to induce a loss of righting reflex. These results support the hypothesis that neuronal networks active in sleep are also involved in the anesthetized state and suggest that sleep deprivation may partly explain the variability in patient response to anesthesia.


2021 ◽  
Vol 15 ◽  
Author(s):  
Emma R. Huels ◽  
Trent Groenhout ◽  
Christopher W. Fields ◽  
Tiecheng Liu ◽  
George A. Mashour ◽  
...  

Studies aimed at investigating brain regions involved in arousal state control have been traditionally limited to subcortical structures. In the current study, we tested the hypothesis that inactivation of prefrontal cortex, but not two subregions within parietal cortex—somatosensory barrel field and medial/lateral parietal association cortex—would suppress arousal, as measured by an increase in anesthetic sensitivity. Male and female Sprague Dawley rats were surgically prepared for recording electroencephalogram and bilateral infusion into prefrontal cortex (N = 13), somatosensory barrel field (N = 10), or medial/lateral parietal association cortex (N = 9). After at least 10 days of post-surgical recovery, 156 μM tetrodotoxin or saline was microinjected into one of the cortical sites. Ninety minutes after injection, rats were anesthetized with 2.5% sevoflurane and the time to loss of righting reflex, a surrogate for loss of consciousness, was measured. Sevoflurane was stopped after 45 min and the time to return of righting reflex, a surrogate for return of consciousness, was measured. Tetrodotoxin-mediated inactivation of all three cortical sites decreased (p < 0.05) the time to loss of righting reflex. By contrast, only inactivation of prefrontal cortex, but not somatosensory barrel field or medial/lateral parietal association cortex, increased (p < 0.001) the time to return of righting reflex. Burst suppression ratio was not altered following inactivation of any of the cortical sites, suggesting that there was no global effect due to pharmacologic lesion. These findings demonstrate that prefrontal cortex plays a causal role in emergence from anesthesia and behavioral arousal.


2019 ◽  
Author(s):  
JN Reimer ◽  
C Schuster ◽  
CG Knight ◽  
DSJ Pang ◽  
VSY Leung

AbstractAn effective and pain-free killing method is required to achieve the goal of euthanasia, a “good death”. Overdose of sodium pentobarbital (PB) by intraperitoneal (IP) injection is a widely accepted technique, but questions remain regarding pain associated with administration. As PB rapidly causes sedation and loss of consciousness, most studies have relied on indirect evidence of pain. The objective of this study was to assess pain associated with IP PB using an appropriate vehicle control.Adult male and female Sprague Dawley (SD) and female Wistar rats (N = 112) were block randomised by sex and strain to receive one of four treatments: 1) 800 mg/kg PB (pH 11); 2) 800 mg/kg PB with 4 mg/kg lidocaine (PB+lido); 3) saline or 4) vehicle controls (pH 11 or 12.5). Behavior (Rat Grimace Scale [RGS], writhing, back arching) was evaluated at baseline, before loss of righting reflex (PB and PB+lido groups), 80s, 151s and 10 min post-injection (PI; saline and vehicle control groups).In the vehicle control groups, the RGS scores were increased at 151s PI (SD: p = 0.0008, 95%CI −0.731 to −0.202) from baseline, as was relative frequency of writhing (SD: p < 0.00001; Wistar; p = 0.0004). RGS scores remained elevated 10 mins PI (SD: p = 0.0070, 95%CI −0.768 to −0.118; Wistar: p = 0.0236, 95%CI −0.907 to −0.0742) but the relative frequency of writhing did not (p > 0.05). The RGS scores and the relative frequency of writhing remained low in the PB, PB+lido and saline groups (p > 0.05). Back arching increased from baseline in the PB+lido group before loss of righting reflex and in the vehicle control group (SD rats) at 151s PI (p < 0.05).These results show that IP PB results in signs associated with pain. The sedative effects of PB limit behavioral assessment.


2021 ◽  
Vol 11 (40) ◽  
pp. 208-208
Author(s):  
Indrani Chakraborty ◽  
Arniban Sukul ◽  
Nirmal Sukul

Potentized Nux Vomica has been reported to produce antialcoholic effect in mice, rats and toads. The effect relates to consumption of alcohol and alcohol-induced loss of righting reflex (RR). RR’s maintain normal erect posture of an animal and are centrally controlled in the midbrain. In the present study young toads, Duttaphrynus melanostictus were first treated with Nux vomica 200 CH and then partially immersed in 209 mM ethanol solution in such a way that their head remained above the level of ethanol solution. Toadlets were removed from the ethanol solution every 10 min, tested for the loss of RR and returned to the ethanol solution. Toadlets were placed in a supine position on a dry flat surface. Failure to right within 60 sec was considered as the loss of RR. The experiment was repeated 10 times. Control toadlets were pretreated with 90% ethanol instead of Nux Vomica 200 CH. The percentages of toadlets showing loss of RR, both in the control as well as in the Nux-treated groups, were shown in graphs against the duration of exposure to ethanol solution. Differences in the percentage distribution between the control and the treatment groups losing RR were tested by χ2 test. All the experiments were conducted at room temperature. The percentage of toadlets losing RR increased with time of exposure to ethanol solution. The increase was significantly higher with the control than with the Nux-treated group. Nux Vomica 200 CH might have influenced the mid-brain of toadlets thereby countering the hypnotic effect of ethanol in the toadlets.


2011 ◽  
Vol 115 (1) ◽  
pp. 36-43 ◽  
Author(s):  
Tao Luo ◽  
L. Stan Leung

Background The brain histaminergic system plays a critical role in maintenance of arousal. Previous studies suggest that histaminergic neurotransmission might be a potential mediator of general anesthetic actions. However, it is not clear whether histaminergic tuberomamillary nucleus (TMN) is necessarily involved in the sedative/hypnotic effects of general anesthetics. Methods Male Long Evans rats underwent either TMN orexin-saporin/sham lesion or implantation of intracerebroventricular cannula 2 weeks before the experiment. The behavioral endpoint of loss of righting reflex was used to assess the hypnotic property of isoflurane, propofol, pentobarbital, and ketamine in animals. Histaminergic cell loss was assessed by adenosine deaminase expression in the TMN using immunohistochemistry. Results Rats with bilateral TMN orexin-saporin lesion induced an average 72% loss of histaminergic cells compared with sham-lesion rats. TMN orexin-saporin lesion or intracerebroventricular administration of triprolidine (an H1 receptor antagonist) decreased the 50% effective concentration for loss of righting reflex value and prolonged emergence time to isoflurane anesthesia. However, TMN orexin-saporin lesion had no significant effect on the anesthetic sensitivity to propofol, pentobarbital, and ketamine. Conclusions These findings suggest a role of the TMN histaminergic neurons in modulating isoflurane anesthesia and that the neural circuits for isoflurane-induced hypnosis may differ from those of γ-aminobutyric acid-mediated anesthetics and ketamine.


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