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PubMed2005

Assessment of ketamine and medetomidine anaesthesia in the domestic rabbit.

OBJECTIVE: To study the effects of ketamine and two doses of medetomidine administered by two routes of injection in a genetically diverse population of rabbits. STUDY DESIGN: Prospective, randomized, clinical trial. ANIMALS: One hundred and five domestic rabbits of mixed breed, sex and age. MATERIALS AND METHODS: Rabbits undergoing orchiectomy or ovariohysterectomy received ketamine (15 mg kg(-1)) combined with medetomidine at 0.25 or 0.5 mg kg(-1), by subcutaneous (SC) or intramuscular (IM) injection. Anaesthesia was supplemented with 1.5-2% isoflurane when signs of regular jaw movements and/or slight limb twitching indicated inadequate anaesthesia. Heart and respiratory rate, blood oxygen saturation, end-tidal carbon dioxide concentration and rectal temperature were monitored at several time points. Duration of surgical anaesthesia and anaesthesia time were measured. At completion of surgery, atipamezole (1.0 or 0.5 mg kg(-1), IM or SC) was administered. STATISTICAL ANALYSES: MANOVA was used to compare variables over time between males and females, anaesthetic doses and routes of drug administration. RESULTS: All reflexes were lost significantly more rapidly after IM drug administration (p < 0.05). The times (in minutes) from drug injection to loss of reflexes for the respective groups were: righting reflex: 6.3 (15.0 + 0.25, SC), 5.5 (15.0 + 0.5, SC), 2.9 (15.0 + 0.25, IM) and 2.3 (15.0 + 0.5, IM); ear pinch: 9.2, 8.5, 4.8, 3.6; pedal withdrawal: 12.8, 10.4, 6.6, 5.2. Heart and respiratory rates during surgery did not differ between groups, however the highest end-tidal CO(2) concentration during surgery was significantly affected by dose, with the highest concentration occurring in group 15.0 + 0.5 IM. The number of animals requiring isoflurane tended to decrease with increasing dose of anaesthetic and significantly more females required supplementation than males (p < 0.05). Recovery from anaesthesia (return of righting reflex) was not significantly different between dose groups (p > 0.1) but was more rapid in animals given IM atipamezole (13.6 +/- 13 versus 21 +/- 17, p = 0.037). No anaesthetic-related mortality occurred and all but three animals recovered uneventfully. Five animals were killed whilst under anaesthesia because of unrelated disease. CONCLUSION AND CLINICAL RELEVANCE: Ketamine-medetomidine combinations reliably produced surgical anaesthesia in domestic rabbits that could easily be deepened for brief periods with low concentrations of isoflurane. Subcutaneous administration was better tolerated, but the speed of induction was slower compared with IM injection. Atipamezole was an effective antagonist and produced most rapid effects when administered IM.

Analgesics, Non-Narcotic↗

PubMed1985

Barbiturate tolerance and dependence: effects on synaptosomal sodium transport and membrane fluidity.

DBA mice were fed lab chow containing phenobarbital for seven or eight days. Upon withdrawal of the phenobarbital diet, dependence was evidenced by appearance of hypothermia, handling-induced convulsions and lethal seizures. Functional tolerance was determined by injecting phenobarbital into mice treated with the phenobarbital diet or a pair-fed control diet and measuring the brain concentration of phenobarbital at the time of loss of righting reflex and the time of regaining righting reflex. Both measures demonstrated that chronic consumption of phenobarbital resulted in functional tolerance. When the diet was withdrawn for two days, tolerance was no longer present, indicating a rapid reversal of the adaptive changes. The veratridine-stimulated uptake of 24Na by isolated brain synaptosomes was used as a measure of membrane function. Sodium uptake was inhibited in vitro by pentobarbital and ethanol, and the inhibitory effects of these drugs were attenuated by chronic in vivo phenobarbital treatment. The fluidity of brain synaptic plasma membranes was estimated by the fluorescence polarization of the fluorescent probe molecules 1-(4-trimethylammonium phenyl)-6-phenyl-1,3,5-hexatriene and 1,6-diphenyl-1,3,5-hexatriene. Synaptic membranes from mice treated chronically with phenobarbital did not differ from those of control mice with regard to either the baseline fluorescence polarization of the probes or the decrease in fluorescence polarization produced by in vitro exposure to phenobarbital or ethanol. Taken together, these results indicate that although chronic phenobarbital ingestion resulted in tolerance and dependence (studied in vivo), and adaptation of sodium channels (studied in vitro), there was no evidence that these changes were due to alterations in the membrane physical properties.

Animals↗

PubMed2002

Attenuation of iminodipropionitrile induced behavioral syndrome by sodium salicylate in rats.

Iminodipropionitrile (IDPN) produces irreversible behavioral abnormalities characterized by excitation with choreiform and circling movements (ECC) syndrome in rodents. Concomitant exposure to drugs or environmental chemicals has been shown to alter IDPN-induced neurobehavioral toxicity. This investigation was undertaken to study the effect of sodium salicylate (SS) on IDPN-induced behavioral abnormalities in rats. The animals were exposed to IDPN (100 mg/kg ip) daily for 8 days. SS was administered daily 30 min before IDPN in the doses of 50, 100 and 200 mg/kg ip for 12 days. The animals were observed for neurobehavioral abnormalities including dyskinetic head movements, circling, tail hanging, air righting reflex and contact inhibition of the righting reflex. Horizontal and vertical locomotor activities and forelimbs grip strength were also measured. After behavioral studies, the animals were sacrificed, and the cerebrum and temporal bones were collected for glutathione analysis and inner ear histopathology, respectively. The onset of ECC syndrome was observed on Day 9 in the IDPN-alone group with 100% incidence on Day 12. Cotreatment with salicylate dose-dependently delayed the onset time and significantly attenuated the incidence and severity of IDPN-induced neurobehavioral signs. IDPN alone significantly increased horizontal motor activity and reduced vertical motor activity and forelimbs grip strength; these effect were significantly reversed by salicylate treatment. Treatment with salicylate also attenuated IDPN-induced depletion of GSH in the cerebrum, suggesting its free radical scavenging property.

Animals↗

PubMedDate not supplied

Exacerbation of iminodipropionitrile-induced behavioral toxicity, oxidative stress, and vestibular hair cell degeneration by gentamicin in rats.

This study describes the effect of gentamicin, an aminoglycoside antibiotic on iminodipropionitrile (IDPN)-induced abnormal neurobehavioral syndrome in female Sprague-Dawley rats. The animals were exposed to IDPN in the dose of 100 mg/kg/day intraperitoneally for 7 days. Gentamicin (GM) was administered intraperitoneally daily 1 h before IDPN in the doses of 10, 40, and 80 mg/kg body weight in three different groups of rats. One more group of animals received gentamicin alone (80 mg/kg) and served as the gentamicin-alone group. The intensity of IDPN induced characteristic excitation with choreiform, and the circling movement (ECC) syndrome was examined using an observational test battery including dyskinetic head movements, circling, tail hanging, air righting reflex, and contact inhibition of the righting reflex on days 6, 8, 10, 12, 19, 26, and 33. The animals for histopathological observation were sacrificed on day 10, whereas the remaining animals that were used for long-term behavioral studies were sacrificed on day 35 for biochemical observations. The blood and brain samples were collected for the analysis of blood urea nitrogen (BUN), serum creatinine, cerebral malondialdehyde (MDA), conjugated dienes, and lipid hydroperoxides, whereas temporal bones were collected for inner ear histopathology. Our results showed that gentamicin significantly and dose dependently exacerbated the incidence and the severity of the IDPN-induced behavioral syndrome. The histopathology of the inner ear demonstrated more severe loss of sensory hair cells in the crista ampullaris of the rats treated with IDPN plus gentamicin compared to the IDPN-alone treated animals. Concomitant treatment with gentamicin also potentiated IDPN-induced increase in free radical indices, suggesting a possible role of oxidative stress in gentamicin-induced aggravation of IDPN toxicity. Further studies are warranted to determine the role of aminoglycosides in nitrile toxicity and drug-induced movement disorders.

Animals↗

PubMed2004

Sodium benzoate attenuates iminodipropionitrile-induced behavioral syndrome in rats.

This study reports the effects of the antioxidant sodium benzoate (SB) on iminodipropionitrile (IDPN)-induced excitation with choreiform and circling (ECC) syndrome in adult female Wistar rats. Rats in four different groups (n=8) received i.p. injections of SB (0, 50, 100 and 200 mg/kg) daily for 10 days. IDPN (100 mg/kg, i.p.) was administered daily 30 min before SB for the first 8 days. Two additional groups served as control (vehicle) and SB alone (200 mg/kg) groups. The animals were observed daily for neurobehavioral abnormalities, including dyskinetic head movements, circling, tail hanging, righting reflex and contact inhibition of the righting reflex, characterized as the ECC syndrome. In the IDPN-alone treated group, the onset of ECC syndrome occurred on day 9 (2 out of 8 rats), whereas none of the animals treated with IDPN plus SB (100 or 200 mg/kg) showed any signs of ECC syndrome on that day. All the animals in the IDPN-alone group developed severe dyskinesia on day 11. Treatment of rats with SB significantly and dose-dependently attenuated IDPN-induced behavioral deficits.

Animals↗

PubMed1996

Allopregnanolone (THP) mediates anesthetic effects of progesterone in rat brain.

Intravenous infusion of the progesterone or that of progesterone 5 alpha-reduced metabolite, 3 alpha-hydroxy-5 alpha-pregnan-20-one (THP), induces the loss of righting reflex in freely moving rats at the doses of 49 +/- 15 mg/kg or 5.6 +/- 2.2 mg/kg, respectively. The recovery time of righting reflex was 71 +/- 12 min and 21 +/- 5 min for progesterone and THP, respectively. The time course of brain concentrations of THP, but not that of progesterone, correlated with the loss and the recovery of righting reflex. The pretreatment of animals with uncompetitive inhibitor of 5 alpha-reductase 17 beta (N,N-diisopropylcarbamoyl)-androst-3-diene-3-carboxylic acid (SKF 105111) significantly reduces the anesthetic activity of progesterone, but not that of THP. Following progesterone infusion brain level of THP in SKF 105111 pretreated rats was 12% that of vehicle-treated control, and the level of progesterone was 160%. No effect of SKF 105111 on brain THP level was detected in animals infused with THP. These results demonstrate that anesthetic effect of progesterone is mediated through its conversion to THP and support the hypothesis that endogenous metabolites of progesterone may be involved in the regulation of behavior in rats.

Anesthetics↗

PubMed1989

The Auto-Tilt Test in patients with positional vertigo and Menière's disease.

As a new method of testing the righting reflex, which has been considered to be closely related to the otolith function, we used the Auto-Tilt Test (ATT) on 24 patients with positional vertigo, on 5 patients with Meniere's disease before and after cochlearendolymphatic shunt, and on 10 normal subjects. The subject is required to stand on an electrically driven tilt board with an autoregulating switch in hand, and to perform bilateral tilt swings of 5 degrees and 10 degrees wearing a helmet with a Head Inclinometer or tilt sensor. The result of this test in patients with positional vertigo revealed the patients had an abnormal labyrinthine reflex and significantly excessive tilt in the return swing from the side of the lesion. In addition, we consistently observed an inaccurate righting reflex, coupled with a diminished sensation of tilt, on the side of the lesion. The results in Meniere's disease patients, followed up before and after surgery, showed that the depressed righting reflex toward the affected side and the tendency to list to the healthy side before surgery, improved after surgery.

Adult↗

PubMed1994

The utility of excitatory amino acid (EAA) antagonists as analgesic agents. I. Comparison of the antinociceptive activity of various classes of EAA antagonists in mechanical, thermal and chemical nociceptive tests.

The present study was performed to assess the utility of excitatory amino acid (EAA) antagonists as analgesia agents. The antinociceptive activity of various classes of EAA antagonists was assessed in mechanical and thermal flexion reflexes tests, as well as in the formalin test. Additional testing assessed the motor dysfunction associated with antinociceptive dose levels of the agents used, by examining placing, grasping and righting reflexes, as well as occurrences of balance loss during locomotion. No antinociceptive activity was observed on any of the nociceptive measures for the non-NMDA receptor antagonists CNQX or L-AP-3. High doses of the non-competitive (PCP-site) NMDA receptor antagonist MK-801 and the allosteric-glycine receptor antagonist 7-CKA produced antinociception on both the mechanical and thermal flexion reflex measures, while a high dose of the competitive NMDA receptor antagonist CPP produced antinociception only on the thermal flexion reflex measure. Hyperalgesic effects on thermal flexion reflexes were obtained with all doses of the polyamine receptor antagonist ARCA, and with the highest dose of the allosteric-glycine receptor antagonist FICA. Formalin nociceptive behaviours were significantly reduced only by high doses of competitive (APV) and non-competitive (MK-801) NMDA receptor antagonists. The doses of EAA receptor antagonists which produced antinociceptive effects on any of the 3 nociceptive tests also produced evidence of motor dysfunction. Both competitive NMDA receptor antagonists (APV and CPP) produced disruptions of placing, grasping and righting reflexes, while 2 of the allosteric-glycine receptor antagonists (7-CKA and DCQX) significantly disrupted placing and righting reflexes.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesics↗

PubMed1996

The effects of (+)-SKF10047 and ketamine hydrochloride on stereotyped behaviour, locomotor activity and ataxia in guinea pig.

Although behavioural studies of the effects of (+/-)-N-allylnormetazocine ((+)-SKF10047) and ketamine hydrochloride have been conducted in many species, there are no data available on their effects in guinea pig. The aim of the present study was to provide an analysis of the effects of these drugs on stereotyped behaviour, locomotor activity, ataxia and righting reflex latency in guinea pigs. (+)-SKF10047 did not produce significant stereotyped behaviour nor locomotor hyperactivity at any of the doses tested (2.5-10.0 mg/kg, i.p). While righting reflex latency was not significantly affected, significant ataxia was produced at the highest (+)-SKF10047 dose used (i.e., 10 mg/kg). The results for ketamine hydrochloride were similar. Neither significant stereotyped behaviour nor locomotor hyperactivity were produced by ketamine at either dose used (12.5 and 25.0 mg/kg, i.p). However, at the lower dose (i.e., 12.5 mg/kg), significant ataxia and a significant impairment of the righting reflex were produced.

Animals↗

PubMed2005

The role of nicotinic inhibition in ketamine-induced behavior.

UNLABELLED: Several anesthetic drugs are nicotinic antagonists at or below levels used for anesthesia, including ketamine and volatile anesthetics. In contrast, propofol does not inhibit nicotinic receptors. To determine the potential behavioral ramifications of nicotinic inhibition by ketamine, we determined the doses of ketamine required to induce immobility, impair the righting reflex, and cause analgesia in the absence and presence of several nicotinic ligands. Propofol was used as a control in similar experiments. When used as a sole anesthetic drug, 383 +/- 22 mg/kg ketamine intraperitoneally (IP) was required for immobility and 180 +/- 17 mg/kg IP impaired righting reflex. Propofol, 371 +/- 34 mg/kg IP, induced immobility whereas 199 mg/kg IP inhibited the righting reflex. Nicotinic antagonists had no effect on the dose of propofol or ketamine required for either end-point. When nociceptive responses were tested at subhypnotic doses, no pronociceptive or antinociceptive phase was identified for propofol, whereas analgesia was induced at ketamine doses larger than 60 mg/kg IP. The broad-spectrum nicotinic antagonist mecamylamine enhanced the analgesic action of ketamine. These findings are different than those seen with volatile anesthetics, where nicotinic inhibition is thought to be responsible for a pronociceptive action. Such a phase is possibly obscured by analgesia induced as a result of N-methyl-d-aspartic acid antagonism by ketamine. IMPLICATIONS: Ketamine and volatile anesthetics, but not propofol, inhibit neuronal nicotinic acetylcholine receptors in clinically relevant concentration ranges. Nicotinic inhibition by ketamine is not related to its immobilizing or sedating effects but may play a role in ketamine's analgesic action.

Anesthetics, Dissociative↗

PubMed1980

Early appearance of methoxyflurane fluorometabolites in mice.

The biotransformation of methoxyflurane produces two fluorometabolites: inorganic fluoride (F) and an acid-labile fluorocompound (OALF). These have been assayed in the serum of male mice 10, 30, and 100 minutes after either ip or sc injections of 0.7 microliter of methoxyflurane (MOF) per gram of body weight, as either the volatile liquid itself or as a 1:10 dilution in corn oil. During the 10- to 100-minute intervals, the mice were observed for loss of the righting reflex. Corn oil dilution significantly altered the production of MOF fluorometabolites, usually decreasing them, but after 100 minutes, the serum concentration of OALF was 25% greater. Loss of righting reflex was also altered; 11 of 18 mice given undiluted MOF experienced it, whereas only 2 of 18 given the diluted agent did. Compared to the tip route, the sc route resulted in less fluoride at all three time intervals, but more of the OALF after 30 and 100 minutes. None of the sc-dosed mice lost his righting reflex.

Animals↗

PubMed1970

Effects of drugs acting alone and in combination on the motor activity of intact mice.

1. When administered to intact white mice, the central depressants-diphenhydramine, promethazine, chlorpromazine, gammahydroxybutyrate, gammabutyrolactone, hyoscine, and pethidine-produced sedation in small doses, but excitement and convulsions in higher doses. When given to mice pretreated with subanaesthetic doses of phenobarbitone these drugs abolished the righting reflex both in convulsant doses (hyoscine excepted) and in non-convulsant doses. These effects are similar to the effects previously observed with local anaesthetics.2. Meprobamate, diazepam and chlorpromazine produced a loss of righting reflex both when given alone and following phenobarbitone. When given alone in higher doses, chlorpromazine induced convulsions.3. The central stimulants bemegride and picrotoxin antagonized the loss of righting reflex produced by phenobarbitone, but nikethamide, caffeine and strychnine did not alter the depressant effects of phenobarbitone.4. On the basis of these and previous studies with intact white mice a tentative classification of drugs having generalized depressant and stimulant effects on the central nervous system was proposed and discussed.

Adjuvants, Anesthesia↗

PubMed1985

Kinetics of drug action in disease states. VII. Effect of experimental renal dysfunction on the pharmacodynamics of ethanol in rats.

This investigation was designed to determine if renal dysfunction is associated with an increased sensitivity to the CNS depressant effect of ethanol. Adult female Lewis rats were given injections of either 2 or 5 mg/kg of uranyl nitrate (saline for controls) or had both ureters ligated (sham operation for controls) to provide different experimental models of renal dysfunction. Normal and renal dysfunction (ureter-ligated) rats were infused i.v. with ethanol at rates of 8.1, 16.3 or 32.6 mg/min; concentrations of ethanol in cerebrospinal fluid, serum and brain at onset of loss of righting reflex were independent of infusion rate in both groups, indicating rapid equilibration of ethanol between the sampling sites and the biophase. Ethanol concentrations in cerebrospinal fluid at onset and offset (after approximately 110 min of sleep) of loss of righting reflex were not significantly different, reflecting negligible acute tolerance development under the experimental conditions. Ethanol concentrations at onset of loss of righting reflex in cerebrospinal fluid, serum and brain of rats with severe renal dysfunction (5 mg/kg of uranyl nitrate-treated and ureterligated groups) were slightly but statistically significantly lower than in normal controls. This difference was relatively much smaller than the difference in phenobarbital concentrations observed in a similar preceding study, which is consistent with the different mechanisms of action of alcohols and barbiturates.

Animals↗

PubMed2003

Pharmacological effects of intravenous melatonin: comparative studies with thiopental and propofol.

BACKGROUND: Possible utility of high-dose i.v. melatonin as an anaesthetic adjuvant has not been studied. This study compared its effects with thiopental and propofol. METHODS: Sprague Dawley rats were assigned to receive bolus or cumulative i.v. doses of melatonin, thiopental or propofol. Righting reflex, hindpaw withdrawal to a noxious stimulus, response to tail clamping and haemodynamic effects were assessed. RESULTS: Melatonin caused a dose-dependent increase in paw withdrawal threshold and the percent of rats displaying loss of the righting reflex. Melatonin was comparable to thiopental and propofol in terms of its rapid onset of hypnosis. The mean ED(50) values for loss of righting reflex were 5.4 (SEM 1.2), 12.5 (1.1) and 178 (1.1) mg kg(-1) for propofol, thiopental and melatonin, respectively. The percent of rats displaying loss of response to tail clamping was greater with propofol than with melatonin (P<0.05). Haemodynamic changes produced by melatonin or propofol were similar in onset and magnitude. CONCLUSIONS: I.V. melatonin can exert hypnotic effects similar to those observed with thiopental and propofol. Melatonin exhibited significant antinociceptive effects but was less effective in abolishing the response to tail clamping.

Adjuvants, Anesthesia↗

PubMed2000

Survey of the effectiveness of stunning procedures used in Spanish pig abattoirs.

Two pig abattoirs (A and B) equipped with an automated head-only and head-to-chest electrical stunning system, and two (C and D) equipped with a manual carbon dioxide stunning system, were evaluated to compare the effectiveness of stunning in a total of 10,454 pigs slaughtered under commercial conditions. In the abattoirs with the electrical stunning system, the percentage of animals that responded to a nose prick was significantly lower (P<0.05) in abattoir B, where a higher current intensity was used (P<0.05), than in abattoir A. No righting reflex was observed in the electrically stunned pigs. In the abattoirs with the carbon dioxide stunning system, the percentage of animals that responded to a nose prick and showed a righting reflex was significantly lower (P<0.05) in abattoir C, where the duration of the carbon dioxide cycle was longer and the interval between discharge from the system to sticking was shorter (P<0.05), than in D. Comparing the electrical and carbon dioxide stunning systems, the pigs stunned with carbon dioxide were significantly more responsive to a nose prick (P<0.05) and 25 per cent of them showed a righting reflex. Under the conditions of the study the fully automated head-only stunning with additional chest electrodes appeared to be more effective and less susceptible to incorrect handling than the manual carbon dioxide stunning system.

Abattoirs↗

PubMed1996

Differential effects of ethanol in adolescent and adult rats.

Alcohol use in children and adolescents is widespread. However, very little is known about the effects of alcohol exposure during this period of postnatal development. The goal of the present study was to compare the relative sensitivity to the sedative effects of alcohol in periadolescent and adult rats. After treatment with either 4 or 5 g/kg ethanol, both 20- and 30-day-old rats regained their righting reflex significantly earlier than 60-day old rats. In 30-day-old rats, serum ethanol concentrations (SECs) were significantly greater at the time of the recovery of the righting reflex than 60-day-old rats. Developmental differences in the effects of ethanol on locomotor activity were also observed. In 60-day-old rats, 2.5 g/kg ethanol generally decreased locomotor activity. Ethanol did not significantly alter locomotor activity in 20- and 30-day-old rats. Finally there were significant developmental differences in the pharmacokinetics of ethanol with a significant delay in the time to peak SECs in 60-day-old rats relative to 20- and 30-day-old rats. These findings indicate that peri-adolescent rats are less sensitive to the sedative effects of ethanol as they recovered their righting reflex earlier and at significantly higher SECs than adult rats.

Age Factors↗

PubMed1985

Involvement of a GABAergic mechanism in the anticonvulsant effect of pentobarbital against maximal electroshock-induced seizures in rats.

The interaction between pentobarbital and other modulators of GABAergic transmission (diazepam, ethanol and progabide) was investigated on maximal electroshock seizures and on the loss of righting reflexes in rats. Pentobarbital, diazepam and ethanol produced a dose-dependent protection against electroshock seizures, with pentobarbital being more potent (3- and 50-times) than diazepam and ethanol. Progabide neither provided protection nor caused loss of righting reflex. Subprotective doses of pentobarbital and diazepam, together or when combined with a single ineffective dose of ethanol or progabide, caused protection against seizures and loss of righting reflex for variable durations, while ethanol and progabide combination did not provide protection. The protective effect of diazepam was antagonized by RO15-1788, picrotoxin and bicuculline pretreatments. The antagonism of pentobarbital protection by a specific GABA receptor antagonist, bicuculline suggests involvement of the GABAergic system in the anticonvulsant effect of pentobarbital. These results indicate that, like diazepam, the anticonvulsant effect of pentobarbital appears to be mediated through a GABAergic mechanism.

Animals↗

PubMed1982

Potencies of inhaled anesthetics and alcohol in mice selectively bred for resistance and susceptibility to nitrous oxide anesthesia.

A selective breeding process designed to produce mice resistant (HI mice) and susceptible (LO mice) to nitrous oxide anesthesia was continued through 10 generations. At the tenth, generation, the nitrous oxide requirements of the HI and LO mice (as measured by the partial pressure of nitrous oxide required to abolish the righting reflex) were separated by more than 0.7 atm. The HI mice also had a higher anesthetic requirement for cyclopropane, enflurane, isoflurane, halothane, and methoxyflurane, as measured by response to a tail-clamp stimulus. HI mice given an intraperitoneal injection of ethanol (4 g/kg) had 44 per cent shorter sleep times and 12 per cent higher blood alcohol levels upon awakening than did LO mice. For nitrogen, argon, cyclopropane, isoflurane, enflurane halothane, and methoxyflurane, we determined the doses at which the righting reflex was abolished in HI and LO mice. The separation in righting-reflex ED-50s between these two lines was inversely related to the lipid solubility of the anesthetic. For the most lipid-soluble anesthetic, methoxyflurane, no significant differences in potency, as measured by the righting-reflux ED50, could be detected between the HI and LO mice. In contrast, the separation in anesthetic requirements, as measured by the tail-clamp ED50, was approximately the same for each of the anesthetics tested.

Anesthesia, Inhalation↗