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Background: Microglia, the primary immune cells of the brain, are implicated in alcohol use disorder. However, it is not known if microglial activation contributes to the transition from alcohol use to alcohol use disorder or is a consequence of alcohol intake., Methods: We investigated the role of microglia in a mouse model of alcohol dependence using a colony stimulating factor 1 receptor inhibitor (PLX5622) to deplete microglia and a chronic intermittent ethanol vapor two-bottle choice drinking procedure. Additionally, we examined anxiety-like behavior during withdrawal. We then analyzed synaptic neuroadaptations in the central nucleus of the amygdala (CeA) and gene expression changes in the medial prefrontal cortex and CeA from the same animals used for behavioral studies., Results: PLX5622 prevented escalations in voluntary alcohol intake and decreased anxiety-like behavior associated with alcohol dependence. PLX5622 also reversed expression changes in inflammatory-related genes and glutamatergic and GABAergic (gamma-aminobutyric acidergic) genes in the medial prefrontal cortex and CeA. At the cellular level in these animals, microglia depletion reduced inhibitory GABA A and excitatory glutamate receptor-mediated synaptic transmission in the CeA, supporting the hypothesis that microglia regulate dependence-induced changes in neuronal function., Conclusions: Our multifaceted approach is the first to link microglia to the molecular, cellular, and behavioral changes associated with the development of alcohol dependence, suggesting that microglia may also be critical for the development and progression of alcohol use disorder., (Copyright © 2020 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Considering that recumbency can lead to a change in localization, detectability of distinct margins and thus measurement of the organs and reconstruction quality, it is of value to evaluate the effect of positioning on the objective evaluation of abdominal organs in computed tomography (CT). The objective of the present study was to evaluate the effect of patient decubitus on adrenal gland CT biometry. For this purpose, 6 clinically healthy adult beagle dogs underwent CT examination in 4 recumbencies. The various adrenal gland's size measurements were performed by 2 observers. Statistical analyses revealed that repeatability and reproducibility was the highest on the ventral and right lateral recumbencies, respectively. Significant differences were found in the left adrenal gland's length between the different positions (P < 0.001) and the left adrenal gland's width of the cranial pole measured in the dorsal plane (P < 0.04). The measurements on the parasagittal images differed significantly for the left adrenal length (P = 0.01), cranial pole height (P = 0.03), the right adrenal gland's lateral limb's length (P = 0.05) and medial limb's caudal poles height (P < 0.01). The caudal pole height of the right adrenal gland's medial limb was significantly different (P < 0.01) in all positions on the transverse images. In addition, the adrenal position differed significantly, except for the left adrenal gland relative to the nearest renal vessel (P = 0.1). According to these results, it is recommended to perform a CT of adrenal glands always in the same recumbency. If adrenal glands are evaluated on images taken in various recumbencies, we suggest relying on the measurements made on transverse plane images., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Accumulating evidence from preclinical and clinical studies has implicated a role for the cytokine IL-6 in a variety of CNS diseases including anxiety-like and depressive-like behaviors, as well as alcohol use disorder. Here we use homozygous and heterozygous transgenic mice expressing elevated levels of IL-6 in the CNS due to increased astrocyte expression and non-transgenic littermates to examine a role for astrocyte-produced IL-6 in emotionality (response to novelty, anxiety-like, and depressive-like behaviors). Our results from homozygous IL-6 mice in a variety of behavioral tests (light/dark transfer, open field, digging, tail suspension, and forced swim tests) support a role for IL-6 in stress-coping behaviors. Ex vivo electrophysiological studies of neuronal excitability and inhibitory GABAergic synaptic transmission in the central nucleus of the amygdala (CeA) of the homozygous transgenic mice revealed increased inhibitory GABAergic signaling and increased excitability of CeA neurons, suggesting a role for astrocyte produced IL-6 in the amygdala in exploratory drive and depressive-like behavior. Furthermore, studies in the hippocampus of activation/expression of proteins associated with IL-6 signal transduction and inhibitory GABAergic mechanisms support a role for astrocyte produced IL-6 in depressive-like behaviors. Our studies indicate a complex and dose-dependent relationship between IL-6 and behavior and implicate IL-6 induced neuroadaptive changes in neuronal excitability and the inhibitory GABAergic system as important contributors to altered behavior associated with IL-6 expression in the CNS., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To evaluate the cardiovascular effects, pharmacokinetic (PK) data and recovery characteristics of an alfaxalone constant rate infusion (CRI) of different duration in dogs at manufacturer's recommended dose rate., Study Design: Experimental, prospective, randomized, crossover study., Animals: Six intact female Beagles., Methods: Following an intravenous alfaxalone bolus (3 mg kg -1 ), anaesthesia was maintained using an alfaxalone CRI at 0.15 mg kg -1 minute -1 for 90 (short CRI) or 180 minutes (long CRI). Venous blood samples were collected to determine the PK profile. Cardiovascular variables and recovery characteristics were evaluated. Recovery was scored on a scale ranging from 0, excellent to 4, bad. A mixed-model statistical approach was used to compare the cardiovascular parameters (global α = 0.05). An analysis of variance was performed to compare PK parameters and recovery times between treatments., Results: No significant difference was noted between protocols for any PK parameter. Volume of distribution at steady state (935.74 ± 170.25 versus 1119.15 ± 190.65 mL kg -1 ), elimination half-life (12 ± 2 versus 13 ± 3 minutes), clearance from the central compartment (26.02 ± 4.41 versus 27.74 ± 5.65 mL kg -1 minute -1 ) and intercompartmental clearance (8.47 ± 4.06 versus 12.58 ± 7.03 mL kg -1 minute -1 ) were comparable for short CRI and long CRI. Cardiovascular variables remained within physiological limits. Mechanical ventilation was necessary (short CRI: n = 1, long CRI: n = 4). The manufacturer's recommended dose rate resulted in a light plane of anaesthesia. No significant differences in recovery times and scores were observed between treatments. The quality of recovery was scored as very poor with both protocols., Conclusions and Clinical Relevance: PK data were similar between long and short infusions of alfaxalone at the manufacturer's recommended dose, with acceptable cardiovascular conditions. Nevertheless, both protocols resulted in a superficial plane of general anaesthesia with poor recovery characteristics., (Copyright © 2019 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Objective: To investigate alfaxalone total intravenous anaesthesia (TIVA) following premedication with methadone combined with acepromazine (ACP) or dexmedetomidine in bitches undergoing ovariohysterectomy., Study Design: Prospective, blinded, randomized, experimental study., Animals: A group of 12 female Beagles., Methods: Dogs were premedicated intravenously with methadone (0.2 mg kg -1 ) combined with ACP (20 μg kg -1 , group AM) or dexmedetomidine (5 μg kg -1 , group DM). Anaesthesia was induced with alfaxalone (2 mg kg -1 ). Anaesthetic maintenance was obtained with an alfaxalone variable rate infusion (VRI) started at 0.15 mg kg -1 minute -1 and adjusted every 5 minutes based on clinical assessment. Mechanical ventilation was initiated when necessary to maintain normocapnia. Anaesthetic monitoring included electrocardiogram, heart rate (HR), invasive diastolic (DAP), systolic (SAP) and mean arterial blood pressure, arterial haemoglobin oxygen saturation, respiratory variables and oesophageal temperature. Data were recorded every 5 minutes. A mixed model statistical approach was used to compare cardiovascular variables within and between groups (α = 0.05). A Wilcoxon rank-sum test was used to compare body temperature, VRI alfaxalone rate, administered rescue analgesia, sedation, induction, intubation, recovery scores and recovery times between treatments., Results: Overall HR, SAP and DAP differed between groups (p = 0.001, 0.016, 0.019, respectively). The mean VRI dose rate of alfaxalone differed between groups DM [0.13 (0.11-0.14) mg kg -1 minute -1 ] and AM [0.18 (0.13-0.19) mg kg -1 minute -1 ; p = 0.030]. Rescue analgesia was administered more in group AM (p = 0.019). No significant difference in recovery times and scores was observed between protocols., Conclusions and Clinical Relevance: Alfaxalone TIVA following dexmedetomidine/methadone premedication produced a more stable plane of anaesthesia to perform ovariohysterectomy than ACP/methadone. A dose reduction of alfaxalone of 27.7% was obtained in group DM compared with group AM. Recovery quality and recovery times were comparable between both groups., (Copyright © 2019 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Subanaesthetic ketamine has recently been established as an effective and rapid treatment for major depressive disorder showing antidepressant effects for up to 1 week on average. The use of repeated ketamine infusions has been put forward to augment and to prolong the antidepressant response and increase the remission rates. The underlying neurobiological mechanisms responsible for ketamine's antidepressant effects remain unclear. Nevertheless, it has been shown, both in dogs and humans, that ketamine can alter neuronal perfusion and therefore neuronal function in brain regions involved in psychiatric and behavioural disorders. Consequently, the aim of the current placebo controlled study was to assess the long-term effects on cerebral perfusion of single and repeated subanaesthetic ketamine infusions in dogs. Twelve healthy, laboratory dogs were scanned at six different time points following single and repeated ketamine administration, using Single Photon Emission Computed Tomography with the radiotracer 99m Tc-hexamethylpropylene amine oxime. We hypothesised that repeated infusions could lead to more prolonged perfusion alterations in brain regions critical for behaviour regulation. We found that repeated subanaesthetic ketamine administration did not result in more prolonged cerebral perfusion alterations compared to a single ketamine administration., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The interleukin-1 system (IL-1) is a prominent pro-inflammatory pathway responsible for the initiation and regulation of immune responses. Human genetic and preclinical studies suggest a critical role for IL-1β signaling in ethanol drinking and dependence, but little is known about the effects of chronic ethanol on the IL-1 system in addiction-related brain regions such as the central amygdala (CeA). In this study, we generated naïve, non-dependent (Non-Dep) and dependent (Dep) male mice using a paradigm of chronic-intermittent ethanol vapor exposure interspersed with two-bottle choice to examine 1) the expression of IL-1β, 2) the role of the IL-1 system on GABAergic transmission, and 3) the potential interaction with the acute effects of ethanol in the CeA. Immunohistochemistry with confocal microscopy was used to assess expression of IL-1β in microglia and neurons in the CeA, and whole-cell patch clamp recordings were obtained from CeA neurons to measure the effects of IL-1β (50 ng/ml) or the endogenous IL-1 receptor antagonist (IL-1ra; 100 ng/ml) on action potential-dependent spontaneous inhibitory postsynaptic currents (sIPSCs). Overall, we found that IL-1β expression is significantly increased in microglia and neurons of Dep compared to Non-Dep and naïve mice, IL-1β and IL-1ra bi-directionally modulate GABA transmission through both pre- and postsynaptic mechanisms in all three groups, and IL-1β and IL-1ra do not alter the facilitation of GABA release induced by acute ethanol. These data suggest that while ethanol dependence induces a neuroimmune response in the CeA, as indicated by increased IL-1β expression, this does not significantly alter the neuromodulatory role of IL-1β on synaptic transmission., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To compare cardiovascular effects and anaesthetic quality of alfaxalone alone or in combination with a fentanyl constant rate infusion (CRI) when used for total intravenous anaesthesia (TIVA) in dogs., Study Design: Prospective, blinded, randomized, experimental study., Animals: A group of 12 intact female dogs., Methods: Following intramuscular dexmedetomidine (10 μg kg -1 ) and methadone (0.1 mg kg -1 ) administration, anaesthesia was induced intravenously with alfaxalone (2 mg kg -1 ) (group AP) or alfaxalone (2 mg kg -1 ) preceded by fentanyl (2 μg kg -1 ) (group AF). Anaesthetic maintenance was obtained with an alfaxalone variable rate infusion (VRI) started at 0.15 mg kg -1 minute -1 (group AP) or an alfaxalone VRI (same starting rate) combined with a CRI of fentanyl (10 μg kg -1 hour -1 ) (group AF). The alfaxalone VRI was adjusted every 5 minutes, based on clinical assessment. Cardiovascular parameters (recorded every 5 minutes) and recovery characteristics (using a numerical rating scale) were compared between groups. A mixed model statistical approach was used to compare the mean VRI alfaxalone dose and cardiovascular parameters between groups; recovery scores were analysed using the Wilcoxon rank-sum test (α = 0.05)., Results: The mean CRI alfaxalone dose for anaesthetic maintenance differed significantly between treatments [0.16 ± 0.01 mg kg -1 minute -1 (group AP) versus 0.13 ± 0.01 mg kg -1 minute -1 (group AF)]. Overall heart rate, systolic, mean and diastolic arterial pressures were lower in group AF than in group AP (p < 0.0001, p = 0.0058, p < 0.0001 and p < 0.0001, respectively. Recovery quality scores did not differ significantly and were poor in both groups., Conclusions and Clinical Relevance: In combination with a fentanyl CRI, an alfaxalone TIVA provides a cardiovascular stable anaesthesia in dogs. The addition of fentanyl results in a significant dose reduction. The quality of anaesthetic recovery remains poor., (Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Background: Corticotropin-releasing factor (CRF) mediates anxiogenic responses by activating CRF type 1 (CRF 1 ) receptors in limbic brain regions. Anxiety is further modulated by the endogenous cannabinoid (eCB) system that attenuates the synaptic effects of stress. In the amygdala, acute stress activates the enzymatic clearance of the eCB N-arachidonoylethanolamine via fatty acid amide hydrolase (FAAH), although it is unclear whether chronic dysregulation of CRF systems induces maladaptive changes in amygdalar eCB signaling. Here, we used genetically selected Marchigian Sardinian P (msP) rats carrying an innate overexpression of CRF 1 receptors to study the role of constitutive upregulation in CRF systems on amygdalar eCB function and persistent anxiety-like effects., Methods: We applied behavioral, pharmacological, and biochemical methods to broadly characterize anxiety-like behaviors and amygdalar eCB clearance enzymes in msP versus nonselected Wistar rats. Subsequent studies examined the influence of dysregulated CRF and FAAH systems in altering excitatory transmission in the central amygdala (CeA)., Results: msPs display an anxious phenotype accompanied by elevations in amygdalar FAAH activity and reduced dialysate N-arachidonoylethanolamine levels in the CeA. Elevations in CRF-CRF 1 signaling dysregulate FAAH activity, and this genotypic difference is normalized with pharmacological blockade of CRF 1 receptors. msPs also exhibit elevated baseline glutamatergic transmission in the CeA, and dysregulated CRF-FAAH facilitates stress-induced increases in glutamatergic activity. Treatment with an FAAH inhibitor relieves sensitized glutamatergic responses in msPs and attenuates the anxiety-like phenotype., Conclusions: Pathological anxiety and stress hypersensitivity are driven by constitutive increases in CRF 1 signaling that dysregulate N-arachidonoylethanolamine signaling mechanisms and reduce neuronal inhibitory control of CeA glutamatergic synapses., (Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Septic peritonitis occurs relatively commonly in dogs. Secondary septic peritonitis is usually associated with perforation of intestines or infected viscera, such as the uterus in pyometra cases. The aim of this study was to evaluate the bacterial flora in the ovarian bursae of intact bitches as a potential source of contamination. One hundred forty dogs, clinically suspected of pyometra, were prospectively enrolled. The control group consisted of 26 dogs that underwent elective ovariohysterectomies and 18 dogs with mammary gland tumors that were neutered at the time of mastectomy. Bacteriology samples were taken aseptically at the time of surgery from the bursae and the uterus in all dogs. Twenty-two dogs that were clinically suspected of pyometra had sterile uterine content ("mucometra" cases); the remaining 118 had positive uterine cultures ("pyometra" cases) and septic peritoneal fluid was present in 10% of these cases. Of the 118 pyometra cases, 9 had unilateral and 15 had bilateral bacterial colonization of their ovarian bursae. However, the bacteria from the ovarian bursa were similar to those recovered from the uterine pus in only half of the cases. Furthermore, positive bursae were also seen in one mucometra dog (unilateral) and in four control dogs (two unilateral and two bilateral). The data illustrate that the canine ovarian bursa can harbor bacteria. The biological importance of these isolations remains unclear., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Down-stream neuronal alterations, including changes in the 5-HT-2A receptor system, play an important role in the etiology and treatment of depression. The present study examined the effect of prolonged opioid treatment on cerebral 5-HT2A receptors. Cerebral 5-HT2A receptor availability was estimated in seven healthy five-year-old female neutered Beagle dogs pre and post 10-day morphine treatment (oral sustained release morphine 20mg twice daily for 10 days) with (123)I-R-91150, a 5-HT2A selective radioligand, and SPECT. 5-HT2A receptor binding indices (BI) for the frontal, parietal, temporal and occipital cortex and the subcortical region were calculated. Statistical analysis was performed using a linear mixed-effect model with treatment as fixed effect and dog as random effect. Morphine treatment significantly (P≤0.05) lowered 5-HT2A BIs in the right and left frontal cortex, the right and left temporal cortex, the right and left parietal cortex, and the subcortical region. The decreased cerebral 5-HT2A receptor availability following prolonged morphine exposure provides further evidence for an interaction between the opioid and serotonergic system., (Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.)

Objective: To compare sedation and antinociception after oral transmucosal (OTM) and intramuscular (IM) administration of a dexmedetomidine-buprenorphine combination in healthy adult cats., Study Design: Randomized, 'blinded' crossover study, with 1 month washout between treatments., Animals: Six healthy neutered female cats, weighing 5.3-7.5 kg., Methods: A combination of dexmedetomidine (40 μg kg(-1) ) and buprenorphine (20 μg kg(-1) ) was administered by either the OTM (buccal cavity) or IM (quadriceps muscle) route. Sedation was measured using a numerical rating scale, at baseline and at various time points until 6 hours after treatment. At the same time points, analgesia was scored using a dynamic and interactive visual analogue scale, based on the response to an ear pinch, and by the cat's response to a mechanical stimulus exerted by a pressure rate onset device. Physiological and adverse effects were recorded, and oral pH measured. Signed rank tests were performed, with significance set at p < 0.05. Data are presented as median and range., Results: There were no differences in sedation or antinociception scores between OTM and IM dosing at any of the time points. Nociceptive thresholds increased after both treatments but without significant difference between groups. Buccal pH remained between 8 and 8.5. Salivation was noted after OTM administration (n = 2) and vomiting after both OTM (n = 4), and IM (n = 3) dosing., Conclusions and Clinical Relevance: In healthy adult cats, OTM administration of dexmedetomidine and buprenorphine resulted in comparable levels of sedation and antinociception to IM dosing. The OTM administration may offer an alternative route to administer this sedative-analgesic combination in cats., (© 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.)

Objective: To investigate the clinical efficacy of four analgesia protocols in dogs undergoing tibial tuberosity advancement (TTA)., Study Design: Prospective, randomized, blinded study., Animals: Thirty-two client owned dogs undergoing TTA-surgery., Methods: Dogs (n = 8 per treatment) received an oral placebo (PM and PRM) or tepoxalin (10 mg kg(-1) ) tablet (TM and TRM) once daily for 1 week before surgery. Epidural methadone (0.1 mg kg(-1) ) (PM and TM) or the epidural combination methadone (0.1 mg kg(-1) )/ropivacaine 0.75% (1.65 mg kg(-1) ) (PRM and TRM) was administered after induction of anaesthesia. Intra-operative fentanyl requirements (2 μg kg(-1) IV) and end-tidal isoflurane concentration after 60 minutes of anaesthesia (Fe'ISO(60) ) were recorded. Post-operative analgesia was evaluated hourly from 1 to 8 and at 20 hours post-extubation with a visual analogue scale (VAS) and the University of Melbourne Pain Scale (UMPS). If VAS > 50 and/or UMPS > 10, rescue methadone (0.1 mg kg(-1) ) was administered IV. Analgesic duration (time from epidural until post-operative rescue analgesia) and time to standing were recorded. Normally distributed variables were analysed with an F-test (α = 0.05) or t-test for pairwise inter-treatment comparisons (Bonferonni adjusted α = 0.0083). Non-normally distributed data were analysed with the Kruskall-Wallis test (α = 0.05 or Bonferonni adjusted α = 0.005 for inter-treatment comparison of post-operative pain scores)., Results: More intra-operative analgesia interventions were required in PM [2 (0-11)] [median (range)] and TM [2 (1-2)] compared to PRM (0) and TRM (0). Fe'ISO(60) was significantly lower in (PRM + TRM) compared to (PM + TM). Analgesic duration was shorter in PM (459 ± 276 minutes) (mean ± SD) and TM (318 ± 152 minutes) compared to TRM (853 ± 288 minutes), but not to PRM (554 ± 234 minutes). Times to standing were longer in the ropivacaine treatments compared to TM., Conclusions and Clinical Relevance: Inclusion of epidural ropivacaine resulted in reduction of Fe'ISO(60) , avoidance of intra-operative fentanyl administration, a longer duration of post-operative analgesia (in TRM) and a delay in time to standing compared to TM., (© 2012 The Authors. Veterinary Anaesthesia and Analgesia. © 2012 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.)

Objective: To evaluate the cardiovascular effects of a preload of hydroxyethylstarch 6% (HES), preceding an epidural administration of ropivacaine 0.75% in isoflurane anaesthetized dogs., Animals: Six female, neutered Beagle dogs (mean 13.3 ± SD 1.0 kg; 3.6 ± 0.1 years)., Study Design: Randomized experimental cross-over study (washout of 1 month)., Methods: Anaesthesia was induced with propofol and maintained with isoflurane in oxygen/air. All dogs were anaesthetized twice to receive either treatment HESR (continuous rate infusion [CRI] of 7 mL kg(-1) HES started 30 minutes [T-30] prior to epidural administration of ropivacaine 0.75% 1.65 mg kg(-1) at T0) or treatment R (no HES preload and similar dose and timing of epidural ropivacaine administration). Baseline measurements were obtained at T-5. Heart rate (HR), mean (MAP), diastolic (DAP) and systolic (SAP) invasive arterial pressures, cardiac output (Lithium dilution and pulse contour analysis) and derived parameters were recorded every 5 minutes for 60 minutes. Statistical analysis was performed on five dogs, due to the death of one dog., Results: Clinically relevant decreases in MAP (<60 mmHg) were observed for 20 and 40 minutes following epidural administration in treatments HESR and R respectively. Significant decreases in MAP and DAP were present after treatment HESR for up to 20 minutes following epidural administration. No significant within-treatment and overall differences were observed for other cardiovascular parameters. A transient unilateral Horner's syndrome occurred in two dogs (one in each treatment). One dog died after severe hypotension, associated with epidural anaesthesia., Conclusions and Clinical Relevance: A CRI of 7 mL kg(-1) HES administered over 30 minutes before epidural treatment did not prevent hypotension induced by epidural ropivacaine 0.75%. Epidural administration of ropivacaine 0.75% in isoflurane anaesthetized dogs was associated with a high incidence of adverse effects in this study., (© 2011 The Authors. Veterinary Anaesthesia and Analgesia. © 2011 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.)

Inflammatory bowel disease (IBD) is an idiopathic chronic inflammatory disease of the stomach, the small intestine and/or the large intestine. Loss of integrity of the intestinal barrier may be an important factor in the pathogenesis of IBD. In dogs, lymphoplasmacytic enteritis (LPE) is one of the recognized forms of IBD. P-glycoprotein (P-gp) is a membrane-bound efflux pump constituting an important component of the intestinal barrier. Changes in P-gp expression at the level of the intestinal barrier may be important in the pathogenesis of canine LPE, as this may lead to variable protection against xenobiotics and bacterial products in the intestine. The aim of the present study was to evaluate the expression of epithelial P-gp in the intestine in dogs with LPE compared with disease-free animals. Formalin-fixed intestinal biopsy samples from 57 dogs with histopathological evidence of LPE were immunolabelled with anti-P-gp antibodies (C494 and C219). Endoscopic biopsy samples of the duodenum and colon from 16 healthy beagles were used as controls. None of the control dogs had P-gp expression in the apical membrane of duodenal enterocytes, but all had P-gp labelling at the colonic epithelial surface. Twenty out of 57 dogs with LPE had P-gp expression at the apical surface membrane of villus epithelial cells in the duodenum, jejunum and/or ileum. Six out of 16 colonic samples from dogs with LPE had decreased P-gp expression at the epithelial surface compared with controls. It is unclear whether these changes in P-gp expression in dogs with LPE are a cause or a consequence of the inflammation. The observed changes could affect bioavailability of therapeutic drugs used in LPE., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objective: To compare the cardiovascular effects of four epidural treatments in isoflurane anaesthetised dogs., Study Design: Prospective, randomized. experimental study., Animals: Six female, neutered Beagle dogs (13.3±1.0 kg), aged 3.6±0.1 years., Methods: Anaesthesia was induced with propofol (8.3±1.1 mg kg(-1)) and maintained with isoflurane in a mixture of oxygen and air [inspiratory fraction of oxygen (FiO(2))=40%], using intermittent positive pressure ventilation. Using a cross-over model, NaCl 0.9% (P); methadone 1% 0.1 mg kg(-1) (M); ropivacaine 0.75% 1.65 mg kg(-1) (R) or methadone 1% 0.1 mg kg(-1) + ropivacaine 0.75% 1.65 mg kg(-1) (RM) in equal volumes (0.23 mL kg(-1)) using NaCl 0.9%, was administered epidurally at the level of the lumbosacral space. Treatment P was administered to five dogs only. Cardiovascular and respiratory variables, blood gases, and oesophageal temperature were recorded at T-15 and for 60 minutes after epidural injection (T0)., Results: Mean overall heart rate (HR in beats minute(-1)) was significantly lower after treatment M (119±16) (p=0.0019), R (110±18) (p< 0.0001) and RM (109±13) (p<0.0001), compared to treatment P (135±21). Additionally, a significant difference in HR between treatments RM and M was found (p=0.04). After both ropivacaine treatments, systemic arterial pressures (sAP) were significantly lower compared to other treatments. No significant overall differences between treatments were present for central venous pressure, cardiac output, stroke volume, systemic vascular resistance, oxygen delivery and arterial oxygen content (CaO(2)). Heart rate and sAP significantly increased after treatment P and M compared to baseline (T-15). With all treatments significant reductions from baseline were observed in oesophageal temperature, packed cell volume and CaO(2) . A transient unilateral Horner's syndrome occurred in one dog after treatment R., Conclusions and Clinical Relevance: Clinically important low sAPs were observed after the ropivacaine epidural treatments in isoflurane anaesthetised dogs. Systemic arterial pressures were clinically acceptable when using epidural methadone., (© 2011 The Authors. Veterinary Anaesthesia and Analgesia © 2011 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.)

Objective: To investigate the cardiovascular effects of epidural romifidine in isoflurane-anaesthetized dogs., Study Design: Prospective, randomized, blinded experiment., Animals: A total of six healthy adult female Beagles aged 1.25 +/- 0.08 years and weighing 12.46 +/- 1.48 (10.25-14.50) kg., Methods: Anaesthesia was induced with propofol (6-9 mg kg(-1)) and maintained with 1.8-1.9% end-tidal isoflurane in oxygen. End-tidal CO(2) was kept between 35 and 45 mmHg (4.7-6.0 kPa) using intermittent positive pressure ventilation. Heart rate (HR), arterial blood pressure and cardiac output (CO) were monitored. Cardiac output was determined using a LiDCO monitor and the derived parameters were calculated. After baseline measurements, either 10 microg kg(-1) romifidine or saline (total volume 1 mL 4.5 kg(-1)) was injected into the lumbosacral epidural space. Data were recorded for 1 hour after epidural injection. A minimum of 1 week elapsed between treatments., Results: After epidural injection, the overall means (+/- standard deviation, SD) of HR (95 +/- 20 bpm), mean arterial blood pressure (MAP) (81 +/- 19 mmHg), CO (1.63 +/- 0.66 L minute(-1)), cardiac index (CI) (2.97 +/- 1.1 L minute(-1) m(-2)) and stroke volume index (SI) (1.38 +/- 0.21 mL beat(-1) kg(-1)) were significantly lower in the romifidine treatment compared with the overall means in the saline treatment [HR (129 +/- 24 bpm), MAP (89 +/- 17 mmHg), CO (3.35 +/- 0.86 L minute(-1)), CI (6.17 +/- 1.4 L minute(-1) m(-2)) and SI (2.21 +/- 0.21 mL beat(-1) kg(-1))]. The overall mean of systemic vascular resistance index (SVRI) (7202 +/- 2656 dynes seconds cm(-5) m(-2)) after epidural romifidine injection was significantly higher than the overall mean of SVRI (3315 +/- 1167 dynes seconds cm(-5) m(-2)) after epidural saline injection., Conclusion: Epidural romifidine in isoflurane-anaesthetized dogs caused significant cardiovascular effects similar to those reportedly produced by systemic romifidine administration., Clinical Relevance: Similar cardiovascular monitoring is required after epidural and systemically administered romifidine. Further studies are required to evaluate the analgesic effects of epidural romifidine.

Observations: A left sided Horner's syndrome (ptosis, prolapse of the nictitating membrane and miosis) was observed in a 4-year-old female, neutered Beagle dog after epidural injection of 0.22 mL kg(-1) ropivacaine (0.75%) in 0.01 mL kg(-1) of saline during isoflurane anaesthesia. Clinical signs disappeared gradually and resolved completely 4 hours and 10 minutes after injection., Conclusions: The epidural injection of 0.22 mL kg(-1) ropivacaine (0.75%) in 0.01 mL kg(-1) of saline during isoflurane anaesthesia caused unilateral (left) Horner's syndrome in a 4-year-old female, neutered Beagle dog.

Objective: To evaluate the cardiopulmonary effects of sufentanil long acting (SLA) in sevoflurane-anaesthetized dogs., Study Design: Randomized prospective study. Animals Forty female dogs (beagles) aged 1-2 years, weighing 11.97 +/- 1.40 kg., Materials and Methods: The dogs were divided into five groups of eight. Two control groups were used: group A received intramuscular (IM), SLA (50 microg kg(-1)) alone, while group B received the SLA vehicle followed by sevoflurane anaesthesia for 90 minutes. In the other groups, SLA (50 microg kg(-1) IM) was given immediately before (group C(0)), 15 minutes before (group D(15)) or 30 minutes (group E(30)) before induction [with intravenous (IV) thiopental] of sevoflurane anaesthesia lasting for 90 minutes. Heart rate, arterial blood pressure, respiratory rate (f(r)), arterial oxygen haemoglobin saturation and end-tidal sevoflurane concentration (Fe'SEVO) were measured every 10 minutes during anaesthesia and at 2, 4 and 24 hours after induction (not Fe'SEVO). Acid-base and blood gas analyses were performed., Results: Sufentanil LA reduced heart rate and increased arterial CO(2) tensions during anaesthesia. Respiratory depression was least in group E(30) compared with groups C(0) and D(15). Bradycardia was present for at least 24 hours. Respiratory rate was least in group B although arterial O(2) and CO(2) tension values were acceptable up to 24 hours after anaesthesia., Conclusions: Pre-anaesthetic medication with SLA moderately aggravated the cardiopulmonary effects of sevoflurane., Clinical Relevance: In spite of a moderate depressant effect on cardiorespiratory parameters, SLA may be of use as pre-anaesthetic medication before sevoflurane anaesthesia in dogs. Intermittent positive pressure ventilation may occasionally be necessary.

Application of animal models of psychostimulant abuse for experimentation in mice is becoming increasingly important for studying the contribution of genetic differences, as well as the roles of selected (targeted) genes, in specific behaviors. The purpose of this study was to investigate strain differences in cocaine self-administration behavior between C57BL/6 x SJL hybrid mice and BALB/cByJ mice. These two strains were chosen because BALB/cByJ mice have a well-developed behavioral pharmacological profile, and hybrid strains on a C57BL/6 background are commonly used for generating transgenic expressing and knockout mutant mice. C57BL/6 x SJL mice dose-dependently acquired cocaine self-administration (1.0 mg/kg/injection but not 0.25 mg/kg/injection) by responding selectively in the active nose-poke hole and maintaining stable levels of daily drug intake; they also exhibited a characteristic inverted-U-shaped cocaine dose-effect function. BALB/cByJ mice failed to acquire cocaine self-administration at either dose under the same test conditions. The strain differences observed in self-administration did not seem to be attributed to other behavioral differences because the two strains exhibited similar amounts of spontaneous nose-poking in the absence of reinforcers, and BALB/cByJ mice responded more than C57BL/6 x SJL mice in a food-reinforced nose-poke operant task. Importantly, the dose-effect function for the motor stimulating effects of cocaine (3.8-30 mg/kg intraperitoneally) suggests enhanced sensitivity but reduced efficacy of cocaine in stimulating motor activity in BALB/cByJ mice relative to the C57BL/6 x SJL hybrid mice. These results indicate that the decreased liability of BALB/cByJ mice to acquire cocaine self-administration is not the result of differences in spontaneous activity or performance, but may reflect different sensitivities to the reinforcing, or rate-disrupting, properties of cocaine. The data support an influence of genetic background in the liability to self-administer cocaine. Thus, a hypothesis is proposed that the decreased liability of BALB/cByJ mice to acquire cocaine self-administration is related to differences in brain monoamine systems linked to the high "emotionality" profile of BALB/c mice in novel or fearful situations, including perhaps cocaine administration.