[기억할 것]
- research question을 설정하고 그에 대답할 수 있는 실험조건을 설계하는 것이 중요하다. 실험조건을 따져보고 결과를 예상하는 것은 그다음이다.
- 경직되지 말자.
- 1년 52주
[research question]
- Rapid-acting? Rapid-acting mechanism?
- long-lasting/sustained effect? repeated?
- Synergy?
- Drug resistance model?
Antidepressant effects of combination of brexpiprazole and fluoxetine on depression-like behavior and dendritic changes in mice after inflammation. Psychopharmacology (Berl). 2017
#rapid acting #LPS model (0.5 mg/kg))
- A combination of brexpiprazole and fluoxetine could promote a rapid antidepressant effect in an inflammation model of depression
- fluoxetine alone did not show an antidepressant effect.
- fluoxetine (10 mg/kg) plus brexpiprazole (0.1 mg/kg) were administered orally. The doses of brexpiprazole (0.1 mg/kg) and fluoxetine (10 mg/kg) were selected as reported previously.
#model #schedule 
- inflammation decreases BDNF in the hippocampus and PFC, but increases BDNF in the NAc, resulting in depression-like behavior in rodents
Effects of antidepressants on alternations in serum cytokines and depressive-like behavior in mice after lipopolysaccharide administration. Pharmacol Biochem Behav. 2013
#Schedule #LPS model (0.5 mg/kg) #timing
- PAH (60 and 120 mg/kg) and fluoxetine (20 mg/kg) were administered intragastrically once daily for 7 consecutive days.
- In the 7th day, LPS (0.5 mg/kg) was injected intraperitoneally 30 min after drug administration.
- Blood samples were collected 90 min after LPS injection to evaluate serum interleukin (IL)-6 and tumor necrosis factor (TNF)-α levels by enzyme-linked immunosorbent assay (ELISA).
- Behavioral tests were measured 24 h after LPS injection.
- After the behavioral tests the prefrontal cortex was rapidly dissected from the brain of the sacrificed mice, then the 5-hydroxytryptamine (5-HT) and norepinephrine (NE) levels in prefrontal cortex were determined by HPLC–MS, and IL-6 and TNF-α mRNA expression was measured using quantitative real-time PCR.
#Open-field test (OFT) #rule out
- In order to rule out any unspecific locomotor effect of PAH on their antidepressant-like effects, the animals were submitted to the open field paradigm.
- LPS administration increased the immobility time in tail suspension test (TST) and forced swimming test (FST) without affecting spontaneous locomotor activity.
Antidepressant-like Effects of Degraded Porphyran Isolated from Porphyra haitanensis. Mol Nutr Food Res. 2021
- ①Acute porphyran decreased the immobility time in both the forced swimming test and tail suspension test, suggesting the antidepressant-like effects.
- ②subchronic porphyran administration reverses depressive-like behaviors in lipopolysaccharide (LPS)-treated mice. *LPS (0.83 mg kg-1)
- ③chronic porphyran attenuated CUMS-induced impairments of hippocampal neurogenesis and spinogenesis by activating BDNF/TrkB/ERK/CREB signaling pathway
#rapd acting #acute #naive #normal #fluoxetine (20 mg/kg - effective)
- Mice were randomly divided into five groups for each behavioral test.
- One hour later, mice were subjected to forced swimming test, tail suspension test, or open-field test, respectively
#subchronic #timing
- Mice were orally administrated with saline, porphyran, or fluoxetine for continuous 7 days. Saline or LPS (0.83 mg kg-1) was intraperitoneally injected 1 h later after the last drug administration on 7th day.
- The sucrose preference test was performed between 12 and 36 h post LPS injection. The open-field test and forced swimming test were performed immediately after the sucrose preference test
- porphyran inhibits NF-𝜿B/NLRP3 signaling, proinflammatory cytokine release, and microglial activation in the hippocampus
- Porphyran decreased the Iba1 positive cells (A) and thus decreased proinflammatory cytokines such as IL-1𝛽 (B), IL-6 (C), and TNF-𝛼 (D) gene expression in the hippocampus.
- for continuous 28 days.
- chronic porphyran treatment activates hippocampal brain derived neurotrophic factor
- (BDNF)/TrkB/ERK/CREB signaling pathway in chronic unpredictable mild stress (CUMS) in mice.
- Novelty-suppressed Feeding Test
- Sucrose trainings were performed to rule out the abnormal animals (sucrose preference less than 70% on average).
Effects of perillaldehyde on alternations in serum cytokines and depressive-like behavior in mice after lipopolysaccharide administration. Pharmacology Biochemistry and Behavior. 2014
Metformin Ameliorates Lipopolysaccharide-Induced Depressive-Like Behaviors and Abnormal Glutamatergic Transmission. biology. 2020
Aging Exacerbates Depressive-like Behavior in Mice in Response to Activation of the Peripheral Innate Immune System. neuropsychopharmacology. 2017
Antidepressant-like Effects of p-Coumaric Acid on LPS-induced Depressive and Inflammatory Changes in Rats. Exp Neurobiol. 2018
Rosiglitazone attenuates lipopolysaccharide-induced depressive-like behavior and cognitive deficits in mice. 2018
Dynamics and correlation of serum cortisol and corticosterone under different physiological or stressful conditions in mice. PLoS One. 2015
#confirmed the presence of cortisol in mouse serum
#forced swimming test #FST #CORT
Behavioral test_LPS (500 µg/kg) i.p injection
ref. Behavioral, inflammatory and neurochemical disturbances in LPS and UCMS-induced mouse models of depression
LPS-stressed mice showed more immobility time in FST and TST, as well as more time in periphery in OFT than UCMS-stressed mice. Further, LPS-stressed mice showed robuster expression and release of TNF-α, IL-1β and IL-6 in serum and depression-related brain areas (prefrontal cortex, hippocampus and striatum) as compared to UCMS-stressed mice.
Sickness behaviour is observed up to 6 h following systemic LPS administration, while depressive-like behaviour is observed 24 h after LPS challenge
Behavioral test_LPS (50, 100 or 200 μg/kg) i.p injection #habiuation #time
ref. Locomotor activity changes following lipopolysaccharide treatment in mice: a multivariate assessment of behavioral tolerance
the novelty of the open field exerted a motivational influence on activity and, in doing so, LPS-treated mice displayed normal activity levels rather than reduced levels, despite being ``sick.'' This may have been due to the ``threatening'' nature of the new environment, and highlights the importance of habituating animals to the open field prior to testing, for comparative purposes both within and between experiments..
lipopolysaccharide (LPS: 50, 100 or 200 μg/kg) or saline vehicle on experimental Days 1, 4 and 7. At 2 h after each treatment, locomotor activity was assessed in a nonnovel, automated open-field apparatus (Digiscan) for 30 min. On Day 1, all horizontal and vertical activity measures were significantly reduced to near zero values by each dose of LPS. Behavioral tolerance to LPS formed rapidly, as locomotor activity of the treated groups did not differ from the control group on Days 4 or 7.
Mice (n = 24) were habituated to the Digiscan apparatus for 1 h, at least 1 day before testing began. This was sufficient exposure to an open field to eliminate novelty effects [31]. Testing was conducted between 12:00 and 15:00 hours. Animals were randomly assigned to treatment groups (n = 6 per group). On Days 1, 4 and 7, mice were weighed, treated with LPS (50, 100 or 200 mg/kg; groups LPS50, LPS100 and LPS200, respectively) or saline vehicle (group Saline). Given that activity decrements were expected in the treatment groups, it was likely that between group differences would become obscured once the saline-treated mice became habituated to the testing apparatus, which typically occurs within 1 h (e.g., Refs. [7,27]). Due to this, mice were returned to their home cages for 2 h postinjection, and then locomotor activity was recorded in the Digiscan apparatus for 30 min and cumulated in 5-min time blocks. An interval of 2 h between injection and testing was used because, at this time, plasma adrenocorticotrophin (ACTH) and corticosterone levels are maximally increased [42,44] and LPS-induced changes in body temperature are close to maximal for the first phase of fever [16]. After each test period, animals were returned to their home cages and their body weights were recorded 24 h after each injection.
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