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Six geriatric dogs of various breeds belonging to either sex presented for various surgical procedures to Teaching Veterinary Clinical Complex, Mannuthy and University Veterinary Hospital, Kokkalai, were selected for the study. On the day of surgery, preanaesthesia was performed with diazepam and butorphanol. After ten minutes of premedication, preoxygenation was carried out for three minutes. Propofol (1 per cent w/v) was administered as a slow bolus, intravenous injection for induction of anaesthesia. Maintenance of surgical plane of anaesthesia was carried out with isoflurane in oxygen using Bain’s circuit system incorporated with isoflurane vapourizer. Haematological and serum biochemical parameters, which were recorded before premedication, ten minutes after commencement of isoflurane and after recovery from general anaesthesia are described here. The present study concluded that the anaesthetic protocol is safe in geriatric animals with regard to haematological and serum biochemical parameters.

Background: The study was conducted to evaluate the cardiopulmonary functions in dog under propofol, ketamine and isoflurane anaesthesia premedicated with dexmedetomidine and butorphanol.Methods: Four groups of dogs (A,B,C and D) comprising of six animals in each groups were premedicated with glycopyrrolate @ 0.01 mg/kg, dexmedetomidine @5ìg/kg IV and Butorphanol @ 0.1mg/kg IV. Induction was done with propofol (A and B) and with ketamine (C and D). The anaesthesia was maintained with isoflurane (A and C), propofol (B) and ketamine (D). The cardiopulmonary functions were recorded at 0 minute (before premedication) and 20 minutes, 40 minutes and 60 minutes. Result: The heart rate decreased significantly in Group B while there was a significant gradual increase in heart rate in Group D. A significant decrease in respiratory rate was observed in all the groups with a lowest value in group D. The systolic pressure decreased significantly in Group A, B and C but in Group D, the systolic pressure decreased initially at 20 minute. The diastolic pressure decreased significantly in Group A and Group B and but in group D, the diastolic pressure decreased at 20 minute. A significant decrease in mean arterial pressure was recorded in Group A, B and C. In Group D, a decrease in the mean arterial pressure was noticed at 20 minute. The SpO2 level remained near the base line values with slight variation in Group A and C where as the values remained at lower level from the base line value in Group B and D. The EtCO2 level showed non-significant changes in Group A and C. In Group B and D, the EtCO2 levels increased non-significantly with the highest value recorded in Group D. The ECG parameters remained within the normal limit with slight variation according to the heart rate.

To improve animal welfare and data quality and reproducibility during research conducted under anaesthesia, anaesthetic depth in laboratory animals must be precisely monitored and controlled. While a variety of methods have been developed to estimate the depth of anaesthesia in humans, such tools for monitoring anaesthetic depth in laboratory animals remain limited. Here we propose an epidural electrocorticogram-based monitoring system that accurately tracks the depth of anesthesia in mice receiving inhalable isoflurane anaesthesia. Several features of the electrocorticogram signals exhibit robust modulation by the concentration of the administered anesthetic, notably, corticocortical coherence serves as an excellent indicator of anaesthetic depth. We developed a gradient boosting regressor framework that utilizes the extracted features to accurately estimate the depth of anaesthesia. Our method for feature extraction and estimation is conducted with a latency of only ten seconds, establishing a system for the real-time tracking of anaesthetic depth in mice., bioRxiv

Background Strangulating small intestinal lesions in the horse have increased morbidity and mortality compared to nonstrangulating obstructions due to mucosal barrier disruption and subsequent endotoxaemia. Objectives To investigate protective effects of dexmedetomidine on small intestinal ischaemia-reperfusion injury in the horse. Study design Randomised, controlled, experimental study. Methods Eighteen systemically healthy horses were randomly assigned to three groups: control, preconditioning, and post-conditioning. During isoflurane anaesthesia, complete ischaemia was induced in a 1-m segment of jejunum for 90 minutes. Horses in the preconditioning and post-conditioning groups received dexmedetomidine (3.5 µg/kg followed by 7 µg/kg/h) before (preconditioning) or after beginning ischaemia (post-conditioning), and during reperfusion. Jejunal biopsies were collected before ischaemia (baseline-1), at the end of the ischaemic period (ischaemia), and 30 minutes after reperfusion (reperfusion-1). Additional biopsies were taken 24 hours after reperfusion from ischaemia-reperfusion-injured jejunum (reperfusion-2). Epithelial injury was scored histologically, and morphometric analyses were used to calculate villus surface area (VSA) denuded of epithelium. Data were analysed using analysis of variance, Kruskal-Wallis and Wilcoxon two-sample tests. Results In the control group, epithelial injury scores and percentage of VSA denudation for ischaemia-reperfusion-injured jejunum were higher compared to baseline-1 at all time points. The ischaemia and both reperfusion samples from the pre- and post-conditioning groups had lower epithelial injury scores and percentage of VSA epithelial denudation compared to the control group, with no difference from baseline-1 at any time point for the preconditioning group. Main limitations Preconditioning has limited application in the clinical setting with naturally occurring strangulating small intestinal lesions. Conclusions Dexmedetomidine was protective for small intestinal ischaemia-reperfusion injury in the horse when administered before or during ischaemia.

Anaesthetic protocols involving the combined use of a sedative agent, medetomidine, and an anaesthetic agent, isoflurane, are increasingly being used in functional magnetic resonance imaging (fMRI) studies of the rodent brain. Despite the popularity of this combination, a standardised protocol for the combined use of medetomidine and isoflurane has not been established, resulting in inconsistencies in the reported use of these drugs. This study investigated the pharmacokinetic detail required to standardise the use of medetomidine and isoflurane in rat brain fMRI studies. Using mass spectrometry, serum concentrations of medetomidine were determined in Sprague-Dawley rats during medetomidine and isoflurane anaesthesia. The serum concentration of medetomidine for administration with 0.5% (vapouriser setting) isoflurane was found to be 14.4 ng/mL (&plusmn, 3.0 ng/mL). The data suggests that a steady state serum concentration of medetomidine when administered with 0.5% (vapouriser setting) isoflurane can be achieved with an initial subcutaneous (SC) dose of 0.12 mg/kg of medetomidine followed by a 0.08 mg/kg/h SC infusion of medetomidine. Consideration of these results for future studies will facilitate standardisation of medetomidine and isoflurane anaesthetic protocols during fMRI data acquisition.

Concerns have been raised about how deeply patients are anaesthetized, and the effects that different depths of anaesthesia may have after recovery. In order to study the anaesthetic drugs per se, and to eliminate the effect of clinical variables, several animal studies have been published. Isoflurane induced transient deficits on spatial memory at low concentrations, affecting the hippocampus. However, the influence of different concentrations of isoflurane on non-spatial memory still needs clarification. Thus, our aim was to study the effects of different depths of anaesthesia (1% and 2% isoflurane) on a non-spatial memory task, the object recognition test, in C57BL/6 adult mice.Twenty-eight 2-month-old C57BL/6 male mice were habituated to the test arena of the object recognition test for 10 min each day over 2 days before anaesthesia. Mice were then randomly allocated in different treatment groups: 1% or 2%, anaesthetized with 1% or 2% of isoflurane, respectively, for 1 h or the control group, which was not anaesthetised. Twenty-four hours after anaesthesia, the animals were placed in an arena with two identical objects and allowed to explore for 10 min-Sample Trial. One hour later, mice were allowed to explore the arena for 10 min in the presence of one of the objects presented in the previous trial (familiar object) and a novel object - Choice Trial. The time spent exploring each object was evaluated by a blinded analysis. The recognition of one object as familiar was detected based on a higher level of exploration of the novel object.Animals that were anaesthetized previously with 2% isoflurane performed at control levels, indicating the recognition of a familiar object in the object recognition task; this contrasted with the results of the group that was anaesthetized with 1% isoflurane.Lighter (1%) rather than deeper (2%) isoflurane anaesthesia may affect non-spatial memory in C57BL/6 male mice. Our results raise awareness of the need for careful consideration of the depth of anaesthesia used, especially the use of light isoflurane anaesthesia, which is often chosen to provide animal immobilization during non-invasive procedures.

The effects of common anaesthetic agents, such as isoflurane or propofol, on the electroencephalogram are well-known. The most characteristic feature is the marked increase in delta power and alpha power resulting in a bimodal power spectrum from light to moderately deep anaesthesia. Here, a case is presented where the power spectrum became trimodal when anaesthesia was lightened towards wake up. The implications of a third mode for depth-of-anaesthesia monitoring are discussed. Its neuro-physiology is unknown, as it has never been reported before.

General anaesthesia administered during the day has previously been shown to phase shift the honey bee clock. We describe a phase response curve for honey bees (n=105) to six hour isoflurane anaesthesia. The honey bee isoflurane PRC is "weak" with a delay portion (maximum shift of -1.88 hours, circadian time 0 - 3) but no advance zone. The isoflurane-induced shifts observed here are in direct opposition to those of light. Furthermore, concurrent administration of light and isoflurane abolishes the shifts that occur with isoflurane alone. Light may thus provide a means of reducing isoflurane-induced phase shifts.

The concept of the modern anaesthesiological technique partial intravenous anaesthesia (PIVA) is by means of infusion of different pharmacological agents as a supplement to inhalation anaesthetics to reduce the concentration of volatile agents maintaining surgical anaesthesia and to decrease their noxious side effects mainly on cardiovascular and respiratory systems. Alpha-2 agonists are agents with frequent use in equine practice either as sedatives or in general anaesthesia PIVA protocols. The most selective amongst them, dexmedetomidine, is characterized by fewer side effects, lower doses, and fast elimination which make it appropriate for application as a continuous rate infusion (CRI). The purpose of this study was to trace out the effects of dexmedetomidine continuous rate infusion (CRI) as part of PIVA using isoflurane on volatile agent requirements, cardiovascular function, respiration and coagulation parameters, and recovery in healthy horses. Six healthy horses with average age 9.0 ± 5.1 year and mean body weight 247.7 ± 71.4 kg were subjected to either 3-hour lasting isoflurane or isoflurane-dexmedetomidine anaesthesia two weeks apart. The main clinical and anaesthesiological parameters were monitored in 10 minutes intervals. Electrolytes, acid-base, blood gases, and coagulation parameters were measured at the beginning and at the end of each anaesthesia. Recovery times and qualities were also recorded. The results showed that, the addition of dexmedetomidine by CRI at 1.75 μg·kg-1·hour-1 to isoflurane anaesthesia slightly reduced isoflurane requirement for maintenance of surgical anaesthesia but had negligible effects on the recovery time and quality. PIVA using dexmedetomidine and isoflurane produced respiratory acidosis similar to isoflurane anaesthesia alone but with significantly more pronounced hypoxaemia and hyperlactaemia. Both investigated anaesthesia protocols did not influence significantly haemocoagulation parameters.

Highlights • Isoflurane anaesthesia increases MGS score in male DBA/2 mice compared to baseline. • Isoflurane anaesthesia alone has no effect on mouse grimace scale score in male CBA mice. • 0.05 mg/kg buprenorphine has no effect on MGS score in either male CBA or DBA/2 mice., Prevention or alleviation of pain in laboratory mice is a fundamental requirement of in vivo research. The mouse grimace scale (MGS) has the potential to be an effective and rapid means of assessing pain and analgesic efficacy in laboratory mice. Preliminary studies have demonstrated its potential utility for assessing pain in mouse models that involve potentially painful procedures. The next step in validation is to determine if the other procedures that are integral to these models, i.e. anaesthesia or analgesia, result in any changes in MGS score which would need to be taken into account when using this tool to assess post-procedural pain. Here, spontaneous behaviour and MGS data for CBA and DBA/2 mice were recorded at baseline and following either isoflurane anaesthesia (suitable to perform abdominal surgery) or 0.05 mg/kg s.c. buprenorphine. In line with previous studies, isoflurane anaesthesia alone had limited effects on the spontaneous behaviour in either strain of mice. Administration of buprenorphine resulted in increased periods of activity e.g. walking and chewing bedding in CBA mice. These effects were not demonstrated in DBA/2 mice. In comparison, buprenorphine alone had no impact on MGS score in either strain of mice, however DBA/2 mice showed a significant increase in MGS score following isoflurane anaesthesia. The presence of this increased MGS score must be taken into account when attempting to use the MGS to assess pain in DBA/2 mice. Further work should be carried out to establish the presence of this isoflurane effect in other strains and the potential influence of gender on the MGS. This further validation is necessary prior to implementation of this technique in clinical scenarios.

Burrowing and nest building are examples of highly motivated innate behaviours in rodents. Assessments based on these behaviours can be used as non-invasive indicators of pain, distress and suffering. In this study, we investigated the effect of three stressful procedures, namely grid floor housing for 24 h, 15 min of isoflurane anaesthesia and an intraperitoneal saline injection daily for three days, on nest building and burrowing in female C57BL/6NTac mice. For burrowing, we also investigated the effect of the presence of a shelter and nesting material (standard home cage enrichment) versus no shelter and nesting material, and whether the test can be performed during normal working hours. Alongside this, we investigated the effect of grid floor, isoflurane anaesthesia and intraperitoneal injections on stress hormone level, body weight, fur status and sucrose preference. The burrowing test was found to be sensitive to 24 h grid floor housing when no shelter but only a cardboard tube was present during testing. The mice burrowed a mean of 21 g less after grid floor housing (P .01). This change was accompanied by decreased sucrose preference (P .01) and body weight (P .01). 15 min of anaesthesia with isoflurane induced changes in the nest building activity test. After exposure to isoflurane the mice built less complex nests (P = .04). This was accompanied by a decrease in sucrose preference (P .01), a decrease in body weight (P .01), and elevated stress hormone levels (P .01). One daily intraperitoneal injection of saline for three days did not result in changes in nest building activity (P .01). We also found that the mice burrowed equal amount during normal working hours and prior to the dark phase, indicating that the burrowing test can be performed during normal working hours instead of prior to the dark phase (P = .62).

Intravenous (IV) administration in mice is predominantly performed via the lateral tail veins. The technique requires adequate training before it can be used safely and routinely. A novel anaesthesia induction chamber has been developed to simplify the treatment and to facilitate IV injection in mice, particularly for untrained personnel. We have assessed the benefits of the chamber in refining IV injection in isoflurane-anaesthetized mice in direct comparison with the common restrainer method on conscious animals. The body weight, nesting behaviour and concentrations of faecal corticosterone metabolites were taken as indicative of distress induced by the various procedures. The results suggest that both methods of tail-vein injection induce similar levels of momentary stress in the animals, revealed by a short-term increase in the levels of stress hormone metabolites in faeces. A temporary reduction of body weight was observed after IV injection under isoflurane anaesthesia but not for conscious mice injected in the common restrainer. We conclude that the severity of tail-vein injection in mice is ‘mild’ for both methods. There was no evidence that refining the procedure by using isoflurane anaesthesia in the induction chamber was associated with any benefit.

This study was conducted to investigate the effects of blood sampling on animal welfare in a total of 60 NTac:SD rats and 72 C57BL/6NTac mice of both sexes. Blood was sampled either by sublingual vein puncture, tail vein puncture or by retrobulbar plexus/sinus puncture under light isoflurane anaesthesia and, additionally, by facial vein puncture in mice. Non-punctured animals as well as isoflurane-anaesthetised animals were used as controls. Pre- and post-puncture sucrose intake (1.5% w/w) was measured in rats, and nest building scores were studied in mice for 24 h post-puncture. Post-puncture activity and anxiety levels of rats and mice were measured using an elevated plus maze test and an open field test. Stress levels 24 h post-puncture were assessed by analysing faecal corticosteroid metabolites. Sucrose intake and faecal corticosteroid levels were not affected by the blood sampling procedures. Rats showed reduced activity in the open field test and an increased level of anxiety in the elevated plus maze test following retrobulbar plexus puncture and isoflurane anaesthesia. In mice, nest building activity was affected in all the groups compared with the control group, except for animals subjected to facial vein puncture. Retrobulbar sinus puncture, tail vein puncture and sublingual puncture in mice resulted in reduced activity and increased anxiety. We conclude that, of the tested methods, puncture of the tail vein and the sublingual vein have the least adverse effects in rats, whereas facial vein puncture had the least adverse effects on the welfare parameters in mice.

BACKGROUND Myopathies are generally considered to increase the risk for succinylcholine-induced hyperkalaemia and may affect the duration of action of neuromuscular blockers. Centronuclear (myotubular) myopathy (CNM) is congenital and produces various degrees of muscular weakness and associated complications such as respiratory failure. The effects of succinylcholine and the potentially lethal consequences of hyperkalaemia on patients with CNM are unknown due to its rarity. One source of information is the dog, as CNM occurs naturally in dogs. Because of its remarkable similarity with the disease in man, canine CNM can serve as a model to further our knowledge of the effects of succinylcholine. OBJECTIVES We examined the kalaemic and neuromuscular effects of succinylcholine in dogs with and without autosomal-recessive CNM. DESIGN A prospective, experimental study. SETTING Anaesthesiology laboratory, College of Veterinary Medicine, Cornell University, New York, USA. PATIENTS Six dogs with autosomal-recessive CNM and six control dogs. INTERVENTIONS Dogs received succinylcholine 0.3 mg kg during isoflurane anaesthesia. MAIN OUTCOME MEASURES Whole blood potassium concentration was measured 5 min before and after succinylcholine administration. Neuromuscular function was measured with acceleromyography and single twitch stimulation. RESULTS All dogs recovered uneventfully from anaesthesia. The increase in potassium concentration [mean (SD)] following succinylcholine was similar between groups: CNM 0.5 (0.4) mmol l and control 0.7 (0.4) mmol l (P = 0.47). Recovery of the single twitch to 25, 75 and 90% was longer in the CNM group (all P

This study evaluated the cardiopulmonary responses during isoflurane (ISO) anaesthesia in llamas.

Background and aims The purpose of this study is to assess the frontal and parietal ECoG spectrum (gamma range) changes during isoflurane and combined xenon-isoflurane anaesthesia in rats. Methods Experiments were carried out on four adult male Sprague-Dawley rats (250-300 g). The anaesthesia was induced with isoflurane and maintained with isoflurane and a xenon-isoflurane mixture. The rats were maintained at two different anaesthetic depths: light (isoflurane anaesthesia) and deep (isoflurane and xenon-isoflurane anaesthesia). The frontal and the parietal cortical activity was assessed by computing the median frequency, spectral edge frequency and functional connectivity between these two areas during light and deep anaesthesia. Results We noticed a decrease in cortical connectivity under deep isoflurane anaesthesia and an increase in connectivity under deep xenon-isoflurane anaesthesia. Moreover, during xenon-isoflurane anaesthesia, a trend of regularity of electro-cortical activity was present compared with isoflurane anaesthesia. Conclusions Xenon-isoflurane deep anaesthesia demonstrated a series of specific ECoG features regarding frontoparietal functional connectivity (gamma range connectivity increase) and regularity of the electrocortical activity compared with isoflurane anaesthesia.

We have investigated gender differences in the effects of cathinone and the interaction with caffeine on temperature and movement activity in Wistar rats. Telemetry probes were implanted in rats under isoflurane anaesthesia, and 7 days later, temperature and activity were recorded in conscious unrestrained animals. Caffeine (10mg/lkg) or vehicle, and 30min later, cathinone (5mg/kg) or vehicle, were injected subcutaneously. Cathinone produced significant and marked increases in activity, and the response to cathinone was significantly greater in female animals. The combination of caffeine and cathinone causes a short lived potentiation followed by a prolonged inhibition of the activity response to cathinone. Cathinone alone had minor effects on temperature. However, the combination of caffeine and cathinone produced a significant acute rise in temperature only in male rats in the 90min after cathinone injection. Hence, cathinone caused greater increases in activity in female than in male rats. Secondly, caffeine produced an initial potentiation followed by a prolonged inhibition of the activity response to cathinone. Thirdly, cathinone in combination with caffeine significantly raised temperature acutely in male but not female rats. These differences highlight the need to carry out gender studies of the actions of stimulants.

Background Animal studies often require reliable measures for anaesthetic drug effects. Lately, EEG-based depth of anaesthesia estimation has been widely applied to rat models. This study investigated the reliability of different EEG spectral properties in revealing awakening from isoflurane anaesthesia in rats. Methods Adult Wistar rats with previously implanted frontal epidural electrodes were anaesthetized using isoflurane. The anaesthesia was slowly lightened until awakening, as observed by the first spontaneous movement, after which anaesthesia was induced again by increasing the isoflurane concentration. EEG was recorded during the recovery and induction periods, and the spectrograms and 23 quantitative spectral parameters used in the depth of anaesthesia estimation were calculated from the signals. Results The awakening was accompanied by a decrease in EEG activity at frequencies below 25 Hz, while the activity at higher frequencies (25–150 Hz) was increased. Whereas the behaviour of parameters used to measure activity in the lower frequencies was subject to variability between animals, the increase in higher frequency activity was more consistent, resulting in a statistically significant change in the relative gamma power parameters at the moment of awakening. Conclusions The increase in frontal relative gamma activity, especially in the 50–150 Hz frequency band, seems to be the most reliable EEG indicator for the awakening of a rat from isoflurane anaesthesia. A number of other spectral measures can also be used to detect this event. However, the role of gamma frequencies in the performance of these parameters is crucial.

Background Restraint of large estuarine crocodiles is potentially dangerous. Neuromuscular blockers and other immobilising drugs have been used with variable results. Medetomidine has been reported as a reliable, repeatable and reversible immobilisation agent in small estuarine crocodilians. Methods and Results Two wild and two farmed male animals, between 3.05 and 4.6 m long, were hand-injected into a triceps muscle with a metabolically scaled medetomidine dosage. Immobilisation occurred within 30 min. At the conclusion of the procedures, 70 min after medetomidine administration, three animals were injected with atipamezole IM into the opposite triceps muscle at a dosage based on body surface area. Reversal occurred within 5 min. The fourth animal was intubated prior to reversal of medetomidine and maintained on isoflurane anaesthesia for a gastrotomy. All animals were monitored closely post recovery and then regularly for at least 1 week. Conclusions Medetomidine at a metabolically scaled dosage delivered IM into the forelimb was effective for immobilising large estuarine crocodiles for at least 40 min. Atipamezole administered at a dosage calculated as a function of surface area effectively reversed this immobilisation.

Objective To investigate the use of the Narcotrend electroencephalogram (EEG) monitor for the assessment of anesthetic depth in horses undergoing xylazine balanced isoflurane anesthesia. Study design Blinded experimental study. Animals Seven healthy warm-blooded horses, aged 10.6 ± 5.9 years, weighing 535 ± 55 kg. Methods Horses were anesthetized for a terminal surgical trial with xylazine, thiopentone, and guaiphenesin for induction and isoflurane and xylazine continuous rate infusion for maintenance. After surgery, an EEG was recorded and processed by the Narcotrend monitor. It displays an index [Narcotrend index (NI)] between 0 and 100, which is supposed to indicate anesthetic depth. This index was recorded and correlated with eight different end tidal (ET) isoflurane concentrations between 0.8 and 2.2 vol%. In addition, anesthetic depth was numerically scored based on common clinical signs with a score of 1 (plane “too deep”) to 4 (plane “too light”). After testing for normal distribution, both clinical scores and NI were correlated with different ET isoflurane concentrations using Spearman rank correlation. Results Correlation of NI with ET isoflurane concentrations was poor (rs = 0.24). The NI ranged between maximal 48 and minimal 13 in the horses. The clinical scores decreased with increasing ET isoflurane concentrations (rs = 0.80). They ranged from 1 to 4 in different horses at the concentrations investigated. Conclusion In this study, the NI did not seem to be useful for assessment of anesthetic depth in horses receiving isoflurane anesthesia balanced with a xylazine constant rate infusion.

There is increasing interest in studying the role of tau hyperphosphorylation associated with memory impairment. We examined the involvement of tau hyperphosphorylation in memory impairment after hypothermia following isoflurane anaesthesia in rats.Adult rats were randomly divided into three groups: the control group received no treatment and others were subjected to 1.5% isoflurane anaesthesia with or without temperature control for 2 h. On the day before anaesthesia and on postanaesthetic days 1, 3 and 7, cognitive functions were assessed in a Y-maze test paradigm. To find the relationship between memory results and tau, we measured the site-specific phosphorylation of tau at Thr-205 and Ser-396 and the activity of protein phosphatase 2A within the hippocampus.The spatial learning and memory of animals with hypothermia were impaired at day 1 after anaesthesia, compared with nonanaesthetized rats. Anaesthesia and hypothermia led to tau hyperphosphorylation at the Thr-205 and Ser-396 epitopes in the hippocampus. There was no significant difference in the protein phosphatase 2A activity between the control and the postanaesthetic rat hippocampal samples, whereas nearly 45% protein phosphatase 2A inhibition was detected in the anaesthetized without temperature maintenance rat samples.Our results indicate that tau phosphorylation is not a direct result of anaesthesia per se, but it is due to anaesthesia-induced hypothermia and this leads to the inhibition of phosphatase activity as well as tau hyperphosphorylation. Tau hyperphosphorylation is associated with the observed deficits in spatial learning and memory following anaesthesia in hypothermic rats.

The mechanisms by which the nucleus accumbens integrates afferent input from limbic and cortical structures have been influential in the development of models of psychiatric disorders such as schizophrenia. Previous studies of the response of nucleus accumbens (Nacb) cells to the stimulation of afferent inputs from hippocampus (HC) and prefrontal cortex (PFC) have demonstrated that PFC throughput can be modulated by preceding HC input. Examination of the post-synaptic potential size has suggested, however, that summation of these inputs is sublinear. All studies to date examining Nacb integration of inputs via stimulation of afferents have been performed in the anaesthetized rat. The present experiments compare the response of Nacb cells to different combinations of PFC and HC stimulation in awake and isoflurane-anaesthetized rats that were chronically implanted with both stimulating and recording electrodes. The results of these experiments suggest that summation of afferent input in the Nacb of the awake rat is predominantly sublinear, with only a minority of neurons demonstrating modulation of PFC inputs by the HC in the awake or the anaesthetized animal. The response profile of many cells changed during anaesthesia when compared to the awake condition, and on average showed suppression to PFC input 50 and 150 ms following HC stimulation while under deep isoflurane anaesthesia. These results suggest that sublinear integration of afferent input from the PFC and HC is the dominant mode of integration of Nacb cells in the awake animal, which has implications for corticostriatal models of psychiatric dysfunction.

Adolescent rodents differ markedly from adults in several neuro-behavioural parameters. Moreover, ‘paradoxical’ responses to psychostimulants have been reported at this age. Thus, we investigated the responses of adolescent (post-natal day, PND, 34 to 43) and adult (PND >60) Sprague–Dawley male rats to the psychostimulant drug methylphenidate (MPH). We used pharmacological magnetic resonance imaging (phMRI) performed at 4.7 T under isoflurane anaesthesia. Following anatomical MRI, axial gradient echo images were collected continuously. After baseline recording (32 min), animals received MPH (0 or 4 mg/kg i.p.) and were recorded for further 32 min. Region-specific changes in the blood-oxygenation level dependent (BOLD) signal were evident as a function of age. As expected, among adults MPH induced an increase of BOLD signal in nucleus accumbens (NAcc) and prefrontal cortex (PFC), with no effects in the hippocampus (Hip). Notably, among adolescents, MPH induced a marked and generalised decrease of BOLD signal, which occurred earlier in NAcc and PFC whilst being delayed in the Hip. Any bias in BOLD responses was excluded by the measurement of physiological parameters. The present findings highlight the utility of phMRI in animal models. The peculiar negative BOLD effect found in adolescent rats may be suggestive of a reduced cerebro-vascular feedback and/or an increased MPH-induced neuronal activation. Data are relevant for a better understanding of brain/behavioural regulation during adolescent development. Moreover, a greater understanding of the differences between adult and adolescent drug responses will aid in the development of a more appropriate age-specific treatment strategy.