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Journal of the American Association For... Mar 2020Studies of visual responses in isoflurane-anesthetized mice often use the sedative chlorprothixene to decrease the amount of isoflurane used because excessive isoflurane...
Studies of visual responses in isoflurane-anesthetized mice often use the sedative chlorprothixene to decrease the amount of isoflurane used because excessive isoflurane could adversely affect light-evoked responses. However, data are not available to justify the use of this nonpharmaceutical-grade chemical. The current study tested whether pharmaceutical-grade sedatives would be appropriate alternatives for imaging pupillary light reflexes. Male 15-wk-old mice were injected intraperitoneally with 1 mg/kg chlorprothixene, 5 mg/kg acepromazine, 10 mg/kg chlorpromazine, or saline. After anesthetic induction, anesthesia maintenance used 0.5% and 1% isoflurane for sedative- and saline-injected mice, respectively. A photostimulus (16.0 log photons cm s; 470 nm) was presented to the right eye for 20 min, during which the left eye was imaged for consensual pupillary constriction and involuntary pupil drift. Time to immobilization, loss of righting reflex, physiologic parameters, gain of righting reflex, and degree of recovery were assessed also. The sedative groups were statistically indistinguishable for all measures. By contrast, pupillary drift occurred far more often in saline-treated mice than in the sedative groups. Furthermore, saline-treated mice took longer to reach maximal pupil constriction than all sedative groups and had lower heart rates compared with chlorpromazine- and chlorprothixene-sedated mice. Full recovery (as defined by purposeful movement, response to tactile stimuli, and full alertness) was not regularly achieved in any sedative group. In conclusion, at the doses tested, acepromazine and chlorpromazine are suitable pharmaceutical-grade alternatives to chlorprothixene for pupil imaging and conceivably other in vivo photoresponse measurements; however, given the lack of full recovery, lower dosages should be investigated further for use in survival procedures.
Topics: Acepromazine; Anesthesia; Animals; Chlorpromazine; Chlorprothixene; Dopamine Antagonists; Isoflurane; Light; Male; Mice; Pharmaceutical Preparations; Reflex, Pupillary
PubMed: 31915106
DOI: 10.30802/AALAS-JAALAS-19-000094 -
Relationship between vestibular hair cell loss and deficits in two anti-gravity reflexes in the rat.Hearing Research Oct 2021The tail-lift reflex and the air-righting reflex in rats are anti-gravity reflexes that depend on vestibular function. To begin identifying their cellular basis, this...
The tail-lift reflex and the air-righting reflex in rats are anti-gravity reflexes that depend on vestibular function. To begin identifying their cellular basis, this study examined the relationship between reflex loss and the graded lesions caused in the vestibular sensory epithelia by varying doses of an ototoxic compound. After ototoxic exposure, we recorded these reflexes using high speed video. The movies were used to obtain objective measures of the reflexes: the minimum angle formed by the nose, the back of the neck and the base of the tail during the tail-lift maneuver and the time to right in the air-righting test. The vestibular sensory epithelia were then collected from the rats and used to estimate the loss of type I (HCI), type II (HCII) and all hair cells (HC) in both central and peripheral parts of the crista, utricle, and saccule. As expected, tail-lift angles decreased, and air-righting times increased, while the numbers of HCs remaining in the epithelia decreased in a dose-dependent manner. The results demonstrated greater sensitivity of HCI compared to HCII to the IDPN ototoxicity, as well as a relative resiliency of the saccule compared to the crista and utricle. Comparing the functional measures with the cell counts, we observed that loss of the tail-lift reflex associates better with HCI than with HCII loss. In contrast, most HCI in the crista and utricle were lost before air-righting times increased. These data suggest that these reflexes depend on the function of non-identical populations of vestibular HCs.
Topics: Animals; Hair Cells, Auditory; Hair Cells, Vestibular; Ototoxicity; Rats; Reflex; Saccule and Utricle; Vestibule, Labyrinth
PubMed: 34481267
DOI: 10.1016/j.heares.2021.108336 -
Epilepsia Jun 2008We demonstrate the establishment and characterization of a novel virus infection-induced seizure model in C57BL/6 mice. (Comparative Study)
Comparative Study
PURPOSE
We demonstrate the establishment and characterization of a novel virus infection-induced seizure model in C57BL/6 mice.
METHODS
C57BL/6 mice were infected with Theiler's murine encephalomyelitis virus (TMEV) or mock infected. Mice were followed for seizures, weight change, body temperature, motor function (righting reflex, rotorod) and neurological manifestations (inflammation [perivascular cuffing], pyknotic neurons, transforming growth factor [TGF]-beta expression).
RESULTS
C57BL/6 mice are susceptible to seizures induced by TMEV infection. Approximately 50% of C57BL/6 mice develop transient afebrile seizures. Motor function and coordination are impaired in seized mice. Pyramidal neuron pyknosis and TGF-beta expression correlate with seizure activity in the hippocampus.
DISCUSSION
The characterization of this model will enable the investigation of viral and immune contributions in the central nervous system to the development of seizure disorders in humans.
Topics: Animals; Brain; Cardiovirus Infections; Epilepsy, Tonic-Clonic; Female; Hippocampus; Immunoenzyme Techniques; Male; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Motor Skills; Neurons; Postural Balance; Reflex; Seizures; Theilovirus; Transforming Growth Factor beta
PubMed: 18325012
DOI: 10.1111/j.1528-1167.2008.01535.x -
American Journal of Veterinary Research Feb 2019To determine the intracoelemic (ICe) dose of alfaxalone required to induce loss of righting reflex (LRR) in garter snakes (Thamnophis sirtalis) and to evaluate the...
OBJECTIVE
To determine the intracoelemic (ICe) dose of alfaxalone required to induce loss of righting reflex (LRR) in garter snakes (Thamnophis sirtalis) and to evaluate the tactile stimulus response in unanesthetized and alfaxalone-anesthetized snakes.
ANIMALS
8 healthy mature garter snakes.
PROCEDURES
During the first of 3 phases, snakes received each of 3 doses (10, 20, and 30 mg/kg) of alfaxalone, ICe, with a 2-week washout period between treatments. Times to LRR and return of righting reflex were determined after each dose. During phase 2, unanesthetized snakes underwent tactile stimulation testing with Semmes-Weinstein monofilaments once daily for 3 consecutive days to determine the baseline tactile pressure required to elicit purposeful movement. During phase 3, snakes were anesthetized with alfaxalone (30 mg/kg, ICe), and the tactile pressure required to induce purposeful movement was assessed at predetermined times after LRR.
RESULTS
Intracoelomic administration of alfaxalone at doses of 10, 20, and 30 mg/kg induced LRR in 0, 5, and 8 snakes, respectively. For snakes with LRR, median time to LRR following the 30-mg/kg dose (3.8 minutes) was significantly shorter than that following the 20-mg/kg dose (8.3 minutes); median time to return of righting reflex did not differ between the 2 doses. Mean ± SD tactile pressure that resulted in purposeful movement in unanesthetized snakes was 16.9 ± 14.3 g. When snakes were anesthetized, the mean tactile pressure that resulted in purposeful movement was significantly increased from baseline at 10, 20, and 30 minutes after LRR.
CONCLUSIONS AND CLINICAL RELEVANCE
Results suggested ICe administration of alfaxalone might be effective for anesthetizing garter snakes.
Topics: Anesthetics; Animals; Colubridae; Male; Pregnanediones; Reflex, Righting
PubMed: 30681355
DOI: 10.2460/ajvr.80.2.144 -
British Journal of Anaesthesia Mar 2024Delayed emergence from general anaesthesia, opioid-induced sedation, and opioid-induced respiratory depression is associated with perioperative complications. We...
Effects of the orexin receptor 2 agonist danavorexton on emergence from general anaesthesia and opioid-induced sedation, respiratory depression, and analgesia in rats and monkeys.
BACKGROUND
Delayed emergence from general anaesthesia, opioid-induced sedation, and opioid-induced respiratory depression is associated with perioperative complications. We characterised the preclinical effects of the orexin receptor 2 (OX2R)-selective agonist danavorexton (TAK-925) on emergence from anaesthesia and reversal of fentanyl-induced sedation, respiratory depression, and analgesia.
METHODS
Emergence from isoflurane- or propofol-induced anaesthesia and fentanyl-induced sedation were investigated by righting reflex, rotarod, and electroencephalography in rats or monkeys. Fentanyl-induced respiratory depression was assessed by arterial blood gas analysis and whole-body plethysmography in rats and monkeys. Analgesia was evaluated using formalin- and skin incision-induced pain models in rats.
RESULTS
Danavorexton shortened emergence from isoflurane- or propofol-induced anaesthesia and from fentanyl-induced sedation at 1 (P=0.005), 3 (P=0.006), and 3 mg kg s.c. (P=0.022), respectively, by righting reflex in rats. Danavorexton (10 mg kg s.c.) accelerated recovery from isoflurane-, propofol- and fentanyl-induced motor impairment in separate rotarod tests in rats (P=0.008, P=0.007, P=0.017, respectively), and reversed anaesthesia and fentanyl-induced delta-power increases. Danavorexton shortened emergence (return of righting reflex) from isoflurane- or propofol-induced anaesthesia at 1 (P=0.002) and 3 mg kg (P=0.004), respectively, in cynomolgus monkeys. Danavorexton (10 mg kg s.c.) reversed fentanyl-induced increase in Pco (P=0.006), and decrease in Po (P=0.015) and pH (P<0.001) in rats, and at 3 mg kg s.c. reversed fentanyl-induced increase in Pco (P=0.007), and decrease in Po (P=0.013) and SO (P=0.036) in monkeys. Danavorexton increased minute volume and tidal volume in fentanyl-treated animals. Danavorexton at ≤10 mg kg s.c. did not compromise fentanyl analgesia in rat formalin- and skin incision-induced pain models.
CONCLUSIONS
Danavorexton promoted recovery from anaesthesia and fentanyl-induced sedation, and antagonised fentanyl-induced respiratory depression without compromising fentanyl analgesia.
Topics: Rats; Animals; Analgesics, Opioid; Propofol; Orexin Receptors; Isoflurane; Haplorhini; Fentanyl; Respiratory Insufficiency; Anesthesia, General; Analgesia; Pain; Formaldehyde; Piperidines; Sulfonamides
PubMed: 38296753
DOI: 10.1016/j.bja.2023.12.032 -
Frontiers in Neural Circuits 2017Although general anesthetics are routinely administered to surgical patients to induce loss of consciousness, the mechanisms underlying anesthetic-induced...
Although general anesthetics are routinely administered to surgical patients to induce loss of consciousness, the mechanisms underlying anesthetic-induced unconsciousness are not fully understood. In rats, we characterized changes in the extradural EEG and intracranial local field potentials (LFPs) within the prefrontal cortex (PFC), parietal cortex (PC), and central thalamus (CT) in response to progressively higher doses of the inhaled anesthetic sevoflurane. During induction with a low dose of sevoflurane, beta/low gamma (12-40 Hz) power increased in the frontal EEG and PFC, PC and CT LFPs, and PFC-CT and PFC-PFC LFP beta/low gamma coherence increased. Loss of movement (LOM) coincided with an abrupt decrease in beta/low gamma PFC-CT LFP coherence. Following LOM, cortically coherent slow-delta (0.1-4 Hz) oscillations were observed in the frontal EEG and PFC, PC and CT LFPs. At higher doses of sevoflurane sufficient to induce loss of the righting reflex, coherent slow-delta oscillations were dominant in the frontal EEG and PFC, PC and CT LFPs. Dynamics similar to those observed during induction were observed as animals emerged from sevoflurane anesthesia. We conclude that the rat is a useful animal model for sevoflurane-induced EEG oscillations in humans, and that coherent slow-delta oscillations are a correlate of sevoflurane-induced behavioral arrest and loss of righting in rats.
Topics: Anesthetics, Inhalation; Animals; Beta Rhythm; Cortical Synchronization; Delta Rhythm; Dose-Response Relationship, Drug; Electrodes, Implanted; Gamma Rhythm; Male; Methyl Ethers; Motor Activity; Muscle, Skeletal; Parietal Lobe; Prefrontal Cortex; Rats, Sprague-Dawley; Reflex, Righting; Sevoflurane; Thalamus
PubMed: 28725184
DOI: 10.3389/fncir.2017.00036 -
Drug and Alcohol Dependence Jun 2012Carisoprodol is a muscle relaxant that acts at the GABA(A) receptor. Concerns about the abuse liability of carisoprodol are increasing, but evidence that carisoprodol...
AIMS
Carisoprodol is a muscle relaxant that acts at the GABA(A) receptor. Concerns about the abuse liability of carisoprodol are increasing, but evidence that carisoprodol produces tolerance and a significant withdrawal syndrome has yet to be established. The purpose of the current study was to determine if repeated administration of carisoprodol produces tolerance and withdrawal signs in a mouse model.
METHODS
Carisoprodol (0, 100, 200, 300, or 500 mg/kg bid, i.p.) was administered to Swiss-Webster mice for 4 days and loss-of-righting reflex was measured 20-30 min following each administration. On the fourth day, bemegride (20 mg/kg), flumazenil (20 mg/kg), or vehicle was administered following carisoprodol and withdrawal signs were measured. Separate groups of mice receiving the same treatment regimen and dose range were tested for spontaneous withdrawal at 6, 12 and 24 h after the last dose of carisoprodol.
RESULTS
The righting reflex was dose-dependently impaired following the first administration of carisoprodol. A 75-100% decrease in the magnitude of the impairment occurred over the four days of exposure, indicating the development of tolerance to the carisoprodol-elicited loss-of-righting reflex. Withdrawal signs were not observed within 24h following spontaneous withdrawal; however, bemegride and flumazenil each precipitated withdrawal within 15-30 min of administration.
CONCLUSIONS
Carisoprodol treatment resulted in tolerance and antagonist-precipitated withdrawal, suggesting it may have an addiction potential similar to that of other long-acting benzodiazepine or barbiturate compounds.
Topics: Animals; Bemegride; Carisoprodol; Central Nervous System Stimulants; Dose-Response Relationship, Drug; Drug Tolerance; Flumazenil; GABA Modulators; Male; Mice; Muscle Relaxants, Central; Physical Stimulation; Posture; Reflex, Startle; Substance Withdrawal Syndrome; Tremor
PubMed: 22055010
DOI: 10.1016/j.drugalcdep.2011.10.010 -
Neurochemical Research Feb 2016Cerebral oxidative stress (OS) contributes to the pathogenesis of hepatic encephalopathy (HE). Existing evidence suggests that systemic administration of L-histidine...
Cerebral oxidative stress (OS) contributes to the pathogenesis of hepatic encephalopathy (HE). Existing evidence suggests that systemic administration of L-histidine (His) attenuates OS in brain of HE animal models, but the underlying mechanism is complex and not sufficiently understood. Here we tested the hypothesis that dipeptide carnosine (β-alanyl-L-histidine, Car) may be neuroprotective in thioacetamide (TAA)-induced liver failure in rats and that, being His metabolite, may mediate the well documented anti-OS activity of His. Amino acids [His or Car (100 mg/kg)] were administrated 2 h before TAA (i.p., 300 mg/kg 3× in 24 h intervals) injection into Sprague-Dawley rats. The animals were thus tested for: (i) brain prefrontal cortex and blood contents of Car and His, (ii) amount of reactive oxygen species (ROS), total antioxidant capacity (TAC), GSSG/GSH ratio and thioredoxin reductase (TRx) activity, and (iii) behavioral changes (several models were used, i.e. tests for reflexes, open field, grip test, Rotarod). Brain level of Car was reduced in TAA rats, and His administration significantly elevated Car levels in control and TAA rats. Car partly attenuated TAA-induced ROS production and reduced GSH/GSSG ratio, whereas the increase of TRx activity in TAA brain was not significantly modulated by Car. Further, Car improved TAA-affected behavioral functions in rats, as was shown by the tests of righting and postural reflexes. Collectively, the results support the hypothesis that (i) Car may be added to the list of neuroprotective compounds of therapeutic potential on HE and that (ii) Car mediates at least a portion of the OS-attenuating activity of His in the setting of TAA-induced liver failure.
Topics: Animals; Carnosine; Liver Failure; Male; Oxidative Stress; Posture; Rats; Rats, Sprague-Dawley; Thioacetamide
PubMed: 26801175
DOI: 10.1007/s11064-015-1821-9 -
Proceedings. Biological Sciences Jul 2019The effects of anthropogenic aquatic noise on marine invertebrates are poorly understood. We investigated the impact of seismic surveys on the righting reflex and...
The effects of anthropogenic aquatic noise on marine invertebrates are poorly understood. We investigated the impact of seismic surveys on the righting reflex and statocyst morphology of the palinurid rock lobster, Jasus edwardsii, using field-based exposure to air gun signals. Following exposure equivalent to a full-scale commercial assay passing within 100-500 m, lobsters showed impaired righting and significant damage to the sensory hairs of the statocyst. Reflex impairment and statocyst damage persisted over the course of the experiments-up to 365 days post-exposure and did not improved following moulting. These results indicate that exposure to air gun signals caused morphological damage to the statocyst of rock lobsters, which can in turn impair complex reflexes. This damage and impairment adds further evidence that anthropogenic aquatic noise has the potential to harm invertebrates, necessitating a better understanding of possible ecological and economic impacts.
Topics: Acoustics; Animals; Female; Firearms; Noise; Palinuridae; Reflex, Righting; Sense Organs
PubMed: 31337309
DOI: 10.1098/rspb.2019.1424 -
Frontiers in Pediatrics 2022Perinatal hypoxic-ischemic encephalopathy (HIE) is a major cause of epilepsy and chronic neurologic morbidity in premature infants. This study aimed to investigate the...
OBJECTIVE
Perinatal hypoxic-ischemic encephalopathy (HIE) is a major cause of epilepsy and chronic neurologic morbidity in premature infants. This study aimed to investigate the characteristics of acute seizures and the pattern of background activity on amplitude-integrated electroencephalography (aEEG) in neonatal rats with HIE.
METHODS
Hypoxia-ischemia (HI) was induced in postnatal day (P) 3 neonatal rats (n = 12) by ligation of the left carotid artery and exposure to airtight hypoxia for 2 h. Data regarding seizure type, frequency, and duration and those related to neurobehavioral development were collected, and the integrated power of background EEG was analyzed to evaluate the effect of HI.
RESULTS
All neonatal rats in the HI group experienced frequent seizures during hypoxia, and 83.3% of rats (10/12) experienced seizures immediately after hypoxia. Seizure frequency and duration gradually decreased with increasing age. The mortality rate of the HI group was 8.33% (1/12); 120 h after HI induction, only 27.3% (3/11) of pups had low-frequency and short-duration electrographic seizures, respectively. HI rats, which presented seizure activities 96 h after HI insult, exhibited an increase in righting reflex time and a decrease in forelimb grip reflex time. Background EEG was significantly inhibited during HI induction and immediately after hypoxia and gradually recovered 72 h after hypoxia.
CONCLUSION
Seizures caused by HI brain damage in premature infants can be simulated in the P3 neonatal rat model.
PubMed: 35463911
DOI: 10.3389/fped.2022.837909