8 research outputs found

    Isoflurane produces antidepressant effects and induces TrkB signaling in rodents

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    A brief burst-suppressing isoflurane anesthesia has been shown to rapidly alleviate symptoms of depression in a subset of patients, but the neurobiological basis of these observations remains obscure. We show that a single isoflurane anesthesia produces antidepressant-like behavioural effects in the learned helplessness paradigm and regulates molecular events implicated in the mechanism of action of rapid-acting antidepressant ketamine: activation of brain-derived neurotrophic factor (BDNF) receptor TrkB, facilitation of mammalian target of rapamycin (mTOR) signaling pathway and inhibition of glycogen synthase kinase 3 beta (GSK3 beta). Moreover, isoflurane affected neuronal plasticity by facilitating long-term potentiation in the hippocampus. We also found that isoflurane increased activity of the parvalbumin interneurons, and facilitated GABAergic transmission in wild type mice but not in transgenic mice with reduced TrkB expression in parvalbumin interneurons. Our findings strengthen the role of TrkB signaling in the antidepressant responses and encourage further evaluation of isoflurane as a rapid-acting antidepressant devoid of the psychotomimetic effects and abuse potential of ketamine.Peer reviewe

    Daily replacement of very high-fat diet stabilizes food intake and improves mouse welfare by ensuring food quality.

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    Researchers are obligated to ensure food quality and provide laboratory animals with a palatable diet. Factors influencing the quality and palatability of very high-fat diet (VHFD), a widely used rodent diet, however, are understudied. We conducted experiments to establish best practices for ensuring the quality of VHFD and to improve mouse welfare. We found that VHFD in the food hopper was vulnerable first to dehydration and then oxidation within 7-days, leading to dramatic changes in food intake and food preference behavior in mice. Mitigating dehydration and oxidation of VHFD by replacing food daily, rather than weekly, stabilized feeding behavior without effect on overall cardio-metabolic health. Importantly, daily replacement of VHFD also reduced measures of anxiety-like behavior in the open field test. Refining husbandry practices to include daily replacement of VHFD can therefore ensure VHFD quality and improve animal welfare. Standardizing the practice of daily VHFD replacement may also prevent experimental confound and improve experimental reproducibility and replicability

    Ensuring Quality of Very High-Fat Diet (VHFD)

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    Data for "Daily replacement of very high-fat diet stabilizes food intake and improves mouse welfare by ensuring food quality" </p

    Assessing Sleepiness In the Rat: A Multiple Sleep Latencies Test Compared to Polysomnographic Measures of Sleepiness

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    Sleepiness following 6 h of sleep deprivation (SD) was evaluated with a rat multiple sleep latencies test (rMSLT), and the findings were compared to conventional polysomnographic measures of sleepiness. The 6 h of SD was produced by automated activity wheels, and was terminated at either the end of the light period or at the beginning of the dark period. The rMSLT consisted of 5 min wakefulness induced by sensory stimulation followed by 25 min of freedom to sleep. This procedure was repeated every 30 min for 3 h and was designed to minimize the amount of sleep lost due to the testing procedure. In separate rats, 6 h SD was followed by undisturbed recovery, allowing evaluation of conventional polysomnographic measures of sleepiness. Sleep onset latencies were reduced following SD, with recovery in the light (baseline = 8 min, 3 s versus post-SD = 1 min, 17 s) and dark period (baseline = 14 min, 17 s versus 7 min, 7 s). Sleep onset latencies were not altered by varying the duration criterion for the first sleep bout (i.e., sleep bout length criteria of 10, 20, 30, or 60 s were compared). Polysomnographic variables (non-rapid eye movement sleep episode duration, delta power, and number of awakenings) also provided reliable indirect measures of sleepiness, regardless of whether the recovery sleep occurred in the light or dark period. Evaluation of effect size indicated that the rMSLT was a strong measure of sleepiness, and was influenced by homeostatic, circadian, and illumination factors. The rMSLT provided a simple, objective, robust and direct measure of sleepiness that was as effective as conventional polysomnographic measures of sleepiness
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