General Anesthesia In Rats Research Articles

Slack Pathway Deletion Mediates Gamma-Aminobutyric Acid Type A Receptor Reduction in the Effect of Propofol and Isoflurane General Anesthesia in Rats

Slack Pathway Deletion Mediates Gamma-Aminobutyric Acid Type A Receptor Reduction in the Effect of Propofol and Isoflurane General Anesthesia in Rats

Anesthetic Pharmacology of the Mint Extracts L-Carvone and Methyl Salicylate

Introduction: Hydrocarbons with sufficient water solubility allosterically modulate anesthetic-sensitive ion channels. Mint extracts L-carvone and methyl salicylate water solubility exceeds modulation cutoff values for γ-amino butyric acid type A (GABAA) receptors, N-methyl-D-aspartate (NMDA) receptors, and type-2 voltage-gated sodium (Nav1.2) channels. We hypothesized that mint extracts modulate these channels at concentrations that anesthetize rats. Methods: Channels were expressed separately in frog oocytes and studied using 2-electrode voltage clamp techniques at drug concentrations up to 10 mM. Normalized current effects were fit to Hill equations. Mint compounds were formulated in a lipid emulsion and administered IV to rats. When unresponsive to the tail clamp, rats were exsanguinated, and plasma drug concentrations were measured. Results: Both mint compounds caused concentration-dependent inhibition of all channels except for methyl salicylate which inhibited GABAA receptors at low concentrations and potentiated at high concentrations. Plasma drug concentrations in anesthetized rats were 7.9 mM for L-carvone and 2.7 mM for methyl salicylate. This corresponded to ≥53% NMDA receptor inhibition and ≥78% Nav1.2 channel inhibition by both compounds and 30% potentiation of GABAA receptors by methyl salicylate. Conclusion: L-Carvone and methyl salicylate allosterically modulate cell receptor targets important to molecular actions of conventional anesthetics at concentrations that also induce general anesthesia in rats.

Predictive accuracy of CNN for cortical oscillatory activity in an acute rat model of parkinsonism

In neurological and neuropsychiatric disorders neuronal oscillatory activity between basal ganglia and cortical circuits are altered, which may be useful as biomarker for adaptive deep brain stimulation. We investigated whether changes in the spectral power of oscillatory activity in the motor cortex (MCtx) and the sensorimotor cortex (SMCtx) of rats after injection of the dopamine (DA) receptor antagonist haloperidol (HALO) would be similar to those observed in Parkinson disease. Thereafter, we tested whether a convolutional neural network (CNN) model would identify brain signal alterations in this acute model of parkinsonism. A sixteen channel surface micro-electrocorticogram (ECoG) recording array was placed under the dura above the MCtx and SMCtx areas of one hemisphere under general anaesthesia in rats. Seven days after surgery, micro ECoG was recorded in individual free moving rats in three conditions: (1) basal activity, (2) after injection of HALO (0.5 mg/kg), and (3) with additional injection of apomorphine (APO) (1 mg/kg). Furthermore, a CNN-based classification consisting of 23,530 parameters was applied on the raw data. HALO injection decreased oscillatory theta band activity (4–8 Hz) and enhanced beta (12–30 Hz) and gamma (30–100 Hz) in MCtx and SMCtx, which was compensated after APO injection (P ¡ 0.001). Evaluation of classification performance of the CNN model provided accuracy of 92%, sensitivity of 90% and specificity of 93% on one-dimensional signals. The CNN proposed model requires a minimum of sensory hardware and may be integrated into future research on therapeutic devices for Parkinson disease, such as adaptive closed loop stimulation, thus contributing to more efficient way of treatment.

Tiletamine/zolazepam and dexmedetomidine with tramadol provide effective general anesthesia in rats.

BackgroundTiletamine/zolazepam is a dissociative anesthetic combination commonly used in small animals but information is limited in rats. The alpha‐2 agonist, dexmedetomidine, has gained popularity in laboratory animal anesthesia. Tramadol is a weak opioid mu agonist. The aim of this study was to assess whether the tiletamine/zolazepam/dexmedetomidine (ZD) combination effectively provides a surgical anesthesia plane comparable to tiletamine/zolazepam/dexmedetomidine with tramadol (ZDT) in a minor procedure in rats.MethodsRats were induced with ZD or ZDT. After the loss of paw withdrawal, a small incision was made on the rats’ left thighs as a surgical stimulus. Rats were maintained under a surgical anesthesia plane by assessing the loss of the paw withdrawal reflex for 45 minutes, then atipamezole was administered. Monitored anesthesia parameters included: (a) physiological parameters – pulse rate (PR), respiratory rate (RR), tissue oxygen saturation (%SpO2), and body temperature; (b) duration parameters – induction time, onset and duration of surgical anesthesia plane, onset of recovery, and recovery time.ResultsPR was significantly lower at 10 minutes in ZD and 5 minutes in ZDT groups. No difference was observed for RR, %SpO2, and body temperature. Likewise, there were no differences for duration parameters: induction time was less than 3 minutes; onset and duration of surgical anesthesia plane were approximately 5 and 45 minutes, respectively; onset of recovery (time to move) was 51 minutes; and recovery time was 52 minutes, respectively.ConclusionThese data suggest the ZD combination provides a surgical anesthesia plane comparable to ZDT in a rat incisional pain model.

Heart rate variability and heart rate under general anesthesia in rats of both sexes

Heart rate variability and heart rate under general anesthesia in rats of both sexes

Effect of Concurrent Lidocaine, Remifentanil and Methylprednisolone Use on the Clinical Effect of Sugammadex under General Anaesthesia in Rats.

In an in vitro study, lidocaine, remifentanil and methylprednisolone produced inclusion complexes with sugammadex, which lead to a decrease in free and active concentrations of sugammadex. When used concurrently with these drugs, it is likely that the time for sugammadex to reverse a neuromuscular blockade is going to be prolonged due to a synergistic pharmacokinetic or pharmacodynamic interaction. The aim of the present study was to investigate whether concurrent use of sugammadex with remifentanil, lidocaine and methylprednisolone led to a decrease in the neuromuscular blockade reversal effect of sugammadex produced with neuromuscular blockade agent (NMBA) rocuronium. The present study included 42 male Wistar rats. They were randomised into 7 groups, with 6 rats per group. The first group was the control group, the second group received remifentanil and methylprednisolone, the third lidocaine and methylprednisolone, the fourth remifentanil, the fifth lidocaine, the sixth methylprednisolone and the seventh lidocaine and remifentanil. All groups were administered 3.2 mg kg-1 rocuronium for neuromuscular blockade after the administration of study drugs. When the train of four (TOF) value was 0, all groups were administered 16 mg kg-1 sugammadex for the reversal of neuromuscular blockade. With a TOF Watch SX device, the time to TOF ≥0.9 was recorded. When the control group was compared with Groups 3, 4, 5, 6 and 7, no statistically significant difference was found. However, in Group 2, time to TOF ≥0.9 was prolonged significantly when compared with the control group. We suggest that remifentanil and methylprednisolone used concurrently with sugammadex lead to a decrease in sugammadex reversal effect by giving rise to decrease in its free and active concentrations probably via displacement in rats.

Protein malnutrition prevents heat conservation induced by amino acid infusion during general anesthesia in rats

The intravenous administration of an amino acid (AA) mixture during general anesthesia reduces anesthesia-induced hypothermia. AA-induced skeletal muscle protein synthesis and thermogenesis play important roles in the antihypothermic effects of AAs. We hypothesized that a preanesthetic dietary protein deficiency impairs the antihypothermic effects of AAs during general anesthesia due to a reduction in thermogenesis caused by a decrease in muscle protein synthesis. Sprague-Dawley rats were divided into 4 groups: fed a control diet plus saline (CON-SAL) or the AA mixture (CON-AA), and fed a protein-free diet plus saline (PF-SAL) or the AA mixture (PF-AA). SAL solution or AA mixture solution was infused for 180 minutes during sevoflurane anesthesia, and rectal temperatures were measured. Rectal temperatures were significantly higher in the CON-AA group than in the PF-AA group 90 to 180 minutes after initiating the intravenous infusion of the test solutions. There was no significant difference between the PF-SAL and PF-AA groups. Plasma insulin concentrations were significantly higher in the CON-AA group than in the PF-AA group (P < .05). The phosphorylation states of protein kinase B, mammalian target of rapamycin, and eukaryotic initiation factor 4E-binding protein 1 were significantly greater in the CON-AA group than in the PF-AA group (P < .05, P < .05, and P < .01, respectively). Our results indicated that a dietary protein deficiency before general anesthesia impaired the antihypothermic effects of an AA mixture infusion during general anesthesia by decreasing muscle protein synthesis through the insulin-stimulated phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin complex 1 signaling pathway followed by metabolic heat production.

Orexin-1 receptor is involved in ageing-related delayed emergence from general anaesthesia in rats

BackgroundPrevious clinical studies have shown that emergence from isoflurane anaesthesia takes longer in elderly patients compared with middle-aged patients. The current study investigated whether delayed emergence from anaesthesia in older age is associated with the age-related decrease in orexin receptors by using a rat model. MethodsAdult and aged Sprague–Dawley rats were used to assess the time to emergence after 30 min isoflurane anaesthesia (1.4 vol%), and differences in the orexinergic systems, including the number of orexinergic neurones, plasma orexin concentrations, and expression of orexin-1 (OX1R) and orexin-2 receptors, compared using immunofluorescence, radioimmunoassay, western blot, and real-time polymerase chain reaction. The effects of OX1R expression on emergence time were determined by virus-mediated overexpression of OX1R using intra-cerebroventricular injection. ResultsThe median (range) emergence time of aged rats was longer than that in adult rats [1082 (1010–1130) compared with 848 (829–938) s; P=0.0009]. Plasma orexin concentrations were higher in the aged group than the adult group [34 (33–37) and 25 (22–31) pg ml−1, respectively; P=0.04], but the number of orexinergic neurones was similar in both groups. Protein expression of OX1R was lower in the aged group compared with the adult group [0.47 (0.35–0.58) compared with 0.97 (0.86–1.32), respectively; P=0.002]. Overexpression of OX1R significantly shortened the emergence time in aged rats from [1120 (1040–1190) s] to [769 (576–928) s; P=0.03]. ConclusionsAge-related decrease in OX1R expression is associated with delayed emergence from isoflurane anaesthesia in aged rats.

Physostigmine and Methylphenidate Induce Distinct Arousal States During Isoflurane General Anesthesia in Rats.

Although emergence from general anesthesia is clinically treated as a passive process driven by the pharmacokinetics of drug clearance, agents that hasten recovery from general anesthesia may be useful for treating delayed emergence, emergence delirium, and postoperative cognitive dysfunction. Activation of central monoaminergic neurotransmission with methylphenidate has been shown to induce reanimation (active emergence) from general anesthesia. Cholinergic neurons in the brainstem and basal forebrain are also known to promote arousal. The objective of this study was to test the hypothesis that physostigmine, a centrally acting cholinesterase inhibitor, induces reanimation from isoflurane anesthesia in adult rats. The dose-dependent effects of physostigmine on time to emergence from a standardized isoflurane general anesthetic were tested. It was then determined whether physostigmine restores righting during continuous isoflurane anesthesia. In a separate group of rats with implanted extradural electrodes, physostigmine was administered during continuous inhalation of 1.0% isoflurane, and the electroencephalogram changes were recorded. Finally, 2.0% isoflurane was used to induce burst suppression, and the effects of physostigmine and methylphenidate on burst suppression probability (BSP) were tested. Physostigmine delayed time to emergence from isoflurane anesthesia at doses ≥0.2 mg/kg (n = 9). During continuous isoflurane anesthesia (0.9% ± 0.1%), physostigmine did not restore righting (n = 9). Blocking the peripheral side effects of physostigmine with the coadministration of glycopyrrolate (a muscarinic antagonist that does not cross the blood-brain barrier) produced similar results (n = 9 each). However, during inhalation of 1.0% isoflurane, physostigmine shifted peak electroencephalogram power from δ (<4 Hz) to θ (4-8 Hz) in 6 of 6 rats. During continuous 2.0% isoflurane anesthesia, physostigmine induced large, statistically significant decreases in BSP in 6 of 6 rats, whereas methylphenidate did not. Unlike methylphenidate, physostigmine does not accelerate time to emergence from isoflurane anesthesia and does not restore righting during continuous isoflurane anesthesia. However, physostigmine consistently decreases BSP during deep isoflurane anesthesia, whereas methylphenidate does not. These findings suggest that activation of cholinergic neurotransmission during isoflurane anesthesia produces arousal states that are distinct from those induced by monoaminergic activation.

REM sleep disorder following general anesthesia in rats

Postoperative sleep disorders, particularly the REM sleep disorder, may have a significant deleterious impact on postoperative outcomes and may contribute to the genesis of certain delayed postoperative complications.We have followed the effect of distinct anesthesia regimens (ketamine/diazepam vs. pentobarbital) over 6days following the induction of a stable anesthetized state in adult male Wistar rats, chronically instrumented for sleep recording. In order to compare the effect of both anesthetics in the physiological controls vs. the rats with impaired pedunculopontine tegmental nucleus (PPT) cholinergic innervation, during the operative procedure for the implantation of EEG and EMG electrodes, the bilateral PPT lesion was conducted using ibotenic acid (IBO). We have followed in particular post-anesthesia REM sleep.Our results show the distinct EEG microstructure of the motor cortex during the different stable anesthetized states, and their distinct impact on post-anesthesia REM sleep. In contrast to pentobarbital anesthesia, the ketamine/diazepam anesthesia potentiated the long-lasting post-anesthesia REM statewith higher muscle tone (REM1) vs. REM state with atonia (REM2). Whereas both anesthesias prolonged the post-anesthesia REM sleep duration, the long-term prolongation of the REM1 state was demonstrated only after the ketamine/diazepam anesthesia, first due to the increased number of REM1 episodes, and then due to the prolonged REM1 episodes duration. On the other hand, whereas both anesthetic regimens abolished the prolonged post-anesthesia REM/REM1 sleep and the EEG microstructure disorder during REM sleep, only the pentobarbital abolished the increased NREM/REM/NREM transitions, caused by the PPT lesion. In addition, in the PPT lesioned rats, the ketamine/diazepam anesthesia decreased the Wake/NREM/Wake transitions while the pentobarbital anesthesia decreased the Wake/REM/Wake transitions.Our present study suggests pentobarbital anesthesia as being highly beneficial for post-anesthesia REM sleep in the physiological condition as well as during PPT cholinergic neuropathology.

Robust Brain Hyperglycemia during General Anesthesia: Relationships with Metabolic Brain Inhibition and Vasodilation.

Glucose is the main energetic substrate for the metabolic activity of brain cells and its proper delivery into the extracellular space is essential for maintaining normal neural functions. Under physiological conditions, glucose continuously enters the extracellular space from arterial blood via gradient-dependent facilitated diffusion governed by the GLUT-1 transporters. Due to this gradient-dependent mechanism, glucose levels rise in the brain after consumption of glucose-containing foods and drinks. Glucose entry is also accelerated due to local neuronal activation and neuro-vascular coupling, resulting in transient hyperglycemia to prevent any metabolic deficit. Here, we explored another mechanism that is activated during general anesthesia and results in significant brain hyperglycemia. By using enzyme-based glucose biosensors we demonstrate that glucose levels in the nucleus accumbens (NAc) strongly increase after iv injection of Equthesin, a mixture of chloral hydrate and sodium pentobarbital, which is often used for general anesthesia in rats. By combining electrochemical recordings with brain, muscle, and skin temperature monitoring, we show that the gradual increase in brain glucose occurring during the development of general anesthesia tightly correlate with decreases in brain-muscle temperature differentials, suggesting that this rise in glucose is related to metabolic inhibition. While the decreased consumption of glucose by brain cells could contribute to the development of hyperglycemia, an exceptionally strong positive correlation (r = 0.99) between glucose rise and increases in skin-muscle temperature differentials was also found, suggesting the strong vasodilation of cerebral vessels as the primary mechanism for accelerated entry of glucose into brain tissue. Our present data could explain drastic differences in basal glucose levels found in awake and anesthetized animal preparations. They also suggest that glucose entry into brain tissue could be strongly modulated by pharmacological drugs via drug-induced changes in metabolic activity and the tone of cerebral vessels.

Dextroamphetamine (but Not Atomoxetine) Induces Reanimation from General Anesthesia: Implications for the Roles of Dopamine and Norepinephrine in Active Emergence

Methylphenidate induces reanimation (active emergence) from general anesthesia in rodents, and recent evidence suggests that dopaminergic neurotransmission is important in producing this effect. Dextroamphetamine causes the direct release of dopamine and norepinephrine, whereas atomoxetine is a selective reuptake inhibitor for norepinephrine. Like methylphenidate, both drugs are prescribed to treat Attention Deficit Hyperactivity Disorder. In this study, we tested the efficacy of dextroamphetamine and atomoxetine for inducing reanimation from general anesthesia in rats. Emergence from general anesthesia was defined by return of righting. During continuous sevoflurane anesthesia, dextroamphetamine dose-dependently induced behavioral arousal and restored righting, but atomoxetine did not (n = 6 each). When the D1 dopamine receptor antagonist SCH-23390 was administered prior to dextroamphetamine under the same conditions, righting was not restored (n = 6). After a single dose of propofol (8 mg/kg IV), the mean emergence times for rats that received normal saline (vehicle) and dextroamphetamine (1 mg/kg IV) were 641 sec and 404 sec, respectively (n = 8 each). The difference was statistically significant. Although atomoxetine reduced mean emergence time to 566 sec (n = 8), this decrease was not statistically significant. Spectral analysis of electroencephalogram recordings revealed that dextroamphetamine and atomoxetine both induced a shift in peak power from δ (0.1–4 Hz) to θ (4–8 Hz) during continuous sevoflurane general anesthesia, which was not observed when animals were pre-treated with SCH-23390. In summary, dextroamphetamine induces reanimation from general anesthesia in rodents, but atomoxetine does not induce an arousal response under the same experimental conditions. This supports the hypothesis that dopaminergic stimulation during general anesthesia produces a robust behavioral arousal response. In contrast, selective noradrenergic stimulation causes significant neurophysiological changes, but does not promote behavioral arousal during general anesthesia. We hypothesize that dextroamphetamine is more likely than atomoxetine to be clinically useful for restoring consciousness in anesthetized patients, mainly due to its stimulation of dopaminergic neurotransmission.

Ageing delays emergence from general anaesthesia in rats by increasing anaesthetic sensitivity in the brain

Little is known about ageing-related changes in the brain that affect emergence from general anaesthesia. We used young adult and aged Fischer 344 rats to test the hypothesis that ageing delays emergence from general anaesthesia by increasing anaesthetic sensitivity in the brain. Time to emergence was determined for isoflurane (1.5 vol% for 45 min) and propofol (8 mg kg(-1) i.v.). The dose of isoflurane required to maintain loss of righting (LOR) was established in young adult and aged rats. The efficacy of methylphenidate to reverse LOR from general anaesthesia was tested. Separate young adult and aged rats with implanted electroencephalogram (EEG) electrodes were used to test whether ageing increases sensitivity to anaesthetic-induced burst suppression. Mean time to emergence from isoflurane anaesthesia was 47 s [95% CI 33, 60; young adult) compared with 243 s (95% CI 185, 308; aged). For propofol, mean time to emergence was 13.1 min (95% CI 11.9, 14.0; young adult) compared with 23.1 min (95% CI 18.8, 27.9; aged). These differences were statistically significant. When methylphenidate was administered after propofol, the mean time to emergence decreased to 6.6 min (95% CI 5.9, 7.1; young adult) and 10.2 min (95% CI 7.9, 12.3; aged). These reductions were statistically significant. Methylphenidate restored righting in all rats during continuous isoflurane anaesthesia. Aged rats had lower EEG power and were more sensitive to anaesthetic-induced burst suppression. Ageing delays emergence from general anaesthesia. This is due, at least in part, to increased anaesthetic sensitivity in the brain. Further studies are warranted to establish the underlying causes.

Gradual emergence of spontaneous correlated brain activity during fading of general anesthesia in rats: Evidences from fMRI and local field potentials

Intrinsic brain activity is characterized by the presence of highly structured networks of correlated fluctuations between different regions of the brain. Such networks encompass different functions, whose properties are known to be modulated by the ongoing global brain state and are altered in several neurobiological disorders. In the present study, we induced a deep state of anesthesia in rats by means of a ketamine/medetomidine peritoneal injection, and analyzed the time course of the correlation between the brain activity in different areas while anesthesia spontaneously decreased over time. We compared results separately obtained from fMRI and local field potentials (LFPs) under the same anesthesia protocol, finding that while most profound phases of anesthesia can be described by overall sparse connectivity, stereotypical activity and poor functional integration, during lighter states different frequency-specific functional networks emerge, endowing the gradual restoration of structured large-scale activity seen during rest. Noteworthy, our in vivo results show that those areas belonging to the same functional network (the default-mode) exhibited sustained correlated oscillations around 10Hz throughout the protocol, suggesting the presence of a specific functional backbone that is preserved even during deeper phases of anesthesia. Finally, the overall pattern of results obtained from both imaging and in vivo-recordings suggests that the progressive emergence from deep anesthesia is reflected by a corresponding gradual increase of organized correlated oscillations across the cortex.

Method for Single Intravenous Anesthetic Infusion in a Rodent Model

Venous catheterization, endotracheal intubation, and mechanical ventilation are necessary for performing total intravenous general anesthesia in rats. Intubation and IV cannulation of the rat is challenging because of the animals’ small size and the lack of equipment specifically designed for the restricted anatomical dimensions. Here, we present methods for tail venous catheterization and intubation that are quickly learned by the provider with clinical operating room experience but lack experience in the lab. For tail venous catheterization, each rat (n = 20) was gently restrained in a rat chamber; its tail was placed in warm water for 10 minutes, and a 24 gauge intravenous catheter was inserted into the lateral tail vein. The catheter was fixed in place using tape and attached to a T-connector for drug administration. A bolus of propofol (n = 10), ketamine (n = 7), or etomidate (n = 3) was administered to achieve rapid deep anesthesia. Once anesthetized, rats were intubated with the aid of a modified pediatric laryngoscope. The standard miller blade 0 was cut on each side for approximately 2/3 of the total blade length to remove a total of half the width. After the ventilator was properly set, the rats’ vital signs and metabolic status were monitored. Throughout the one-hour infusion, the rats’ physiologic parameters were maintained within normal range. These results indicate that intravenous general anesthesia can be performed effectively and safely in small animals using the refined catheterization and intubation methods tested in this study. These techniques are easily reproducible and learned as they mimic the tools and strategies commonly used in the OR.

Medial septal lesion enhances general anesthesia response

Electrolytic lesion of the medial septum, a basal forebrain nucleus that projects to the hippocampus, prolonged the emergence from general anesthesia in rats. Septal lesioned rats required a longer time to recover from a loss of righting reflex (LORR) and a loss of tail-pinch response after injectable (20mg/kg i.p. pentobarbital, 5mg/kg i.v. propofol) or volatile (1.5% halothane, 2% isoflurane) anesthetic. When incremental doses of propofol were given i.p., septal lesioned rats as compared to control rats showed LORR at a lower dose of propofol. Similarly, when the rats were exposed to increasing concentrations of isoflurane, the percent of rats showing LORR was leftward shifted for lesioned rats as compared to control rats. Septal lesioned rats as compared to control rats showed decreased locomotor activity when exposed to 1.5% halothane. Lesion of the medial septum was confirmed by thionin-stained histological sections as well as loss of acetylcholinesterase (AchE) staining in the hippocampus, indicating a depletion of septohippocampal cholinergic afferents. Medial septal lesion resulted in a near complete loss of hippocampal theta rhythm during walking and a general decrease in power of the hippocampal EEG at all frequencies (0–100Hz), during walking or immobility. It is concluded that lesion of medial septum, in part through a loss of septohippocampal cholinergic afferents, increased the anesthesia response to volatile and injectable general anesthetics, during both induction and emergence. It is suggested that the septohippocampal system participates in many components of general anesthesia including hypnosis, immobility, and analgesia.

Getting Oil and Water to Mix

Getting Oil and Water to Mix

Role of coerulean noradrenergic neurones in general anaesthesia in rats

Central noradrenergic neurones have a role in alertness, analgesia, and thermoregulation; these neurones are also involved in the mechanism of anaesthesia. Locus coeruleus neurones innervate various central nervous regions including the cerebral cortex and hippocampus, and are responsible for wakefulness and analgesia. We hypothesized that these neurones are also involved in both activation of the γ-aminobutyric acid type A (GABA(A)) receptor and inhibition of N-methyl-d-aspartate (NMDA) receptor-mediated anaesthesia. Forty-seven male rats were used to compare duration of anaesthesia before and 10 days after noradrenergic neurone depletion after intraperitoneal (i.p.) administration of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4; 0, 5, and 50 mg kg(-1)). The animals received i.p. thiopental (GABA anaesthetic, 45 mg kg(-1)) or ketamine (NMDA anaesthetic, 100 mg kg(-1)). We also tested the effects of coerulean noradrenergic neurone depletion on i.p. ketamine analgesia (15 mg kg(-1)) using the hot-plate test in a further 21 male rats. At the end of each experiment, norepinephrine contents in the cerebral cortex and hippocampus were measured. I.P. DSP-4 5 and 50 mg kg(-1) significantly decreased ketamine anaesthesia duration by 12.7% and 22.4%, increased thiopental anaesthesia duration by 10.8% and 24.5%, and reduced ketamine-increased hot-plate latency by 55.2% and 68.1%, respectively. In addition, i.p. DSP-4 5 and 50 mg kg(-1) significantly reduced norepinephrine contents in coerulean brain regions by ∼20% and ∼75%, respectively. There were significant correlations between norepinephrine contents in coerulean brain regions and anaesthesia durations and ketamine analgesia. The present data indicate that coerulean noradrenergic neurones may be responsible for both GABA- and NMDA-mediated anaesthetic actions.

Preoperative carbohydrate-rich beverage reduces hypothermia during general anesthesia in rats

Intraoperative hypothermia is associated with several unfavorable events; therefore, it is important to prevent the development of hypothermia. Amino acid consumption and/or infusion have been reported to prevent hypothermia. We hypothesized that preoperative carbohydrate-rich beverage (Arginaid Water™) loading can reduce intraoperative hypothermia in rats under general anesthesia. We divided 18 rats into 3 groups (group A, 8 mL/kg of saline; group B, 8 mL/kg of a carbohydrate-rich beverage; and group C, 21 mL/kg of the carbohydrate-rich beverage). The rats were administered each beverage at the above mentioned doses via an oral gastric tube 30 min before the induction of anesthesia. During the 2-h general anesthesia, rectal temperature was measured at 20-min intervals. Serum ketone body concentration was measured at 0 and 120 min. The baseline temperature was not significantly different among the groups. At the end of the experiment, group A showed a significantly greater decrease in temperature from the baseline (5.4 ± 0.8°C) than group B (3.9 ± 0.7°C, P = 0.01) and group C (3.8 ± 0.8°C, P = 0.01). The temperatures in groups B and C were not significantly different. There was no significant change in the serum ketone body concentration from the baseline at the end of the experiment in group A. However, the serum ketone body concentrations in group B and group C were significantly decreased from the baseline. Preoperative carbohydrate loading reduces hypothermia in rats under general anesthesia.

The Effects of Neuropeptide S on General Anesthesia in Rats

Neuropeptide S (NPS) and its receptor (NPSR) is a novel neuropeptide system that regulates arousal and anxiety. A link between natural sleep and general anesthesia has been suggested. Therefore, we hypothesized that the NPS neuronal system may also modulate general anesthesia. The effects of intracerebroventricular NPS and [D-Cys(tBu)(5)]NPS, a peptide NPSR antagonist, on ketamine and thiopental anesthesia time were measured in rats. Anesthesia time was defined as the interval between the loss of righting reflex and its recovery. Intracerebroventricular NPS 1 to 30 nmol significantly reduced ketamine anesthesia time, showing a bell-shaped dose-response curve. [D-Cys(tBu)(5)]NPS 20 nmol antagonized NPS 1 nmol effects and was per se able to increase ketamine anesthesia time. Similar results were obtained investigating thiopental anesthesia time that was significantly reduced by NPS and prolonged by [D-Cys(tBu)(5)]NPS. NPS via selective NPSR activation stimulates the wakefulness-promoting pathway, thus reducing anesthesia duration. The endogenous NPS/NPSR system seems to tonically control these pathways.