scholarly journals Energizing effects of bupropion on effortful behaviors in mice under positive and negative test conditions: modulation of DARPP-32 phosphorylation patterns

Author(s):  
Carla Carratalá-Ros ◽  
Régulo Olivares-García ◽  
Andrea Martínez-Verdú ◽  
Edgar Arias-Sandoval ◽  
John D. Salamone ◽  
...  

AbstractMotivational symptoms such as anergia, fatigue, and reduced exertion of effort are seen in depressed people. To model this, nucleus accumbens (Nacb) dopamine (DA) depletions are used to induce a low-effort bias in rodents tested on effort-based decision-making. We evaluated the effect of the catecholamine uptake blocker bupropion on its own, and after administration of tetrabenazine (TBZ), which blocks vesicular storage, depletes DA, and induces depressive symptoms in humans. Male CD1 mice were tested on a 3-choice-T-maze task that assessed preference between a reinforcer involving voluntary physical activity (running wheel, RW) vs. sedentary activities (sweet food pellet intake or a neutral non-social odor). Mice also were tested on the forced swim test (FST), two anxiety-related measures (dark–light box (DL), and elevated plus maze (EPM)). Expression of phosphorylated DARPP-32 (Thr34 and Thr75) was evaluated by immunohistochemistry as a marker of DA-related signal transduction. Bupropion increased selection of RW activity on the T-maze. TBZ reduced time running, but increased time-consuming sucrose, indicating an induction of a low-effort bias, but not an effect on primary sucrose motivation. In the FST, bupropion reduced immobility, increasing swimming and climbing, and TBZ produced the opposite effects. Bupropion reversed the effects of TBZ on the T-maze and the FST, and also on pDARPP32-Thr34 expression in Nacb core. None of these manipulations affected anxiety-related parameters. Thus, bupropion improved active behaviors, which were negatively motivated in the FST, and active behaviors that were positively motivated in the T-maze task, which has implications for using catecholamine uptake inhibitors for treating anergia and fatigue-like symptoms.

2021 ◽  
pp. 1-7
Author(s):  
Dylan J. Terstege ◽  
Debra S. MacDonald ◽  
R. Andrew Tasker

Abstract Objective: Ginsenosides, biologically active components of the root of Panax ginseng, have been reported to have therapeutic benefits in a number of disease states including psychiatric conditions such as major depressive disorder. Our objective was to determine if a standardised commercial ginseng extract, G115®, could reduce the signs of behavioural despair commonly observed in animal models of depression either alone or in combination with the selective serotonin reuptake inhibitor (SSRI) fluoxetine. Methods: Male Sprague-Dawley (SD) rats (N = 51) were divided into four groups: vehicle control, G115® ginseng root extract, fluoxetine and fluoxetine plus G115®. Rats were trained to voluntarily consume treatments twice daily for 14 days and were then tested in an open field (OF), elevated plus maze (EPM) and forced swim test (FST). Post-mortem hippocampal and prefrontal cortex tissue was analysed for expression of brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) by western blot. Results: One-way Analysis of Variance revealed no significant group differences in the OF or plus-maze performance on any variable examined. In the FST, fluoxetine significantly reduced immobility time and increased latency to immobility. The effects of fluoxetine were further significantly potentiated by co-administration of G115®. Post-mortem tissue analysis revealed significant group differences in BDNF expression in the left hippocampus and left prefrontal cortex without any accompanying changes in TrkB expression. Conclusions: We conclude that oral G115® significantly potentiates the antidepressant-like effect of fluoxetine in the FST in the absence of potentially confounding effects on locomotion and anxiety.


Author(s):  
Jessica MacGregor

gene in humans have been shown to predict non-responsiveness to antidepressant drugs; suggesting that FGF2 is required for antidepressants to work. In this study, we hypothesized that antidepressants will not work in rodents that lack the FGF2 gene. Hence, we tested antidepressant treatment in transgenic mice that had the FGF2 gene knocked out. Chronic unpredictable stress (CUS) has been used for several decades to produce a reliable depressive and anxious phenotype in mice. This study followed a CUS paradigm and used fluoxetine (Prozac) as antidepressant treatment. Mice received daily fluoxetine administration beginning on week three of CUS and continued until the end of week five to provide an antidepressant effect and reverse the effects of stress. To test for levels of anxiety and depression, a battery of behavioral tests was conducted which began from the least stressful (i.e. sucrose preference test, open field maze, elevated plus maze) to the most stressful test (forced swim test) to prevent testing carry-over effects. AnyMaze software was used to measure behavior in the open field and elevated plus mazes by recording the amount of time each mouse spent in certain parts of the maze. Future studies will examine brain changes associated with FGF2 gene deletion – particularly in astrocyte cells – which might be necessary for successful antidepressant action. Hopefully, this will elucidate novel therapeutic targets for antidepressant and anti-anxiety medication. 


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Hideaki Sato ◽  
Masako Tsukamoto-Yasui ◽  
Satoko Ueno ◽  
Keiko Matsunaga ◽  
Akihiko Kitamura

Abstract Objectives Increase of elderly people, dementia and cognitive decline has been already one of the social problems all over the world. There are a lot of risk factors including dietary composition. Several studies have reported the importance of protein for maintaining brain functions in the elderly, but the details are not well understood. To clarify the relationship between protein intake and brain function in the elderly, we evaluated the effect of low protein diet on cognitive function and psychiatric symptoms in aged mice. Methods Male mice at 60 weeks of age were fed a control diet (NPD; casein 20%) or a low protein diet (LPD; casein 5%). To evaluate neurobehavioral abnormality, we performed the elevated plus maze task (Day 64) and Passive avoidance task (conditioning: Day 66, evaluation: Day 67). Cerebral cortex tissues and plasma were measured for free amino acid concentration by LC-MSMS method, and monoamine concentration in cerebral cortex was measured by HPLC method. Results In the Passive avoidance task, LPD group decreased the time to keep staying in the light box and the rate of individuals entering the dark box during the test period. In the elevated plus maze task, LPD group significantly increased in the number of entry and staying times in open arm. In addition, total travel distance was significantly increased. Moreover, LPD decreased the concentration of not only amino acid in plasma and cerebral cortex but also neurotransmitter such as Glutamate, GABA, Aspartate, Glycine, Dopamine, Norepinephrine, Serotonin. Conclusions We found that long-term intake of low-protein diet occurred memory loss and anxiety like behavior in elderly mice. Intracerebral neurotransmitters are mainly synthesized from amino acids, which is transferred from blood, within the brain. Therefore, behavioral change observed in LPD group might be induced by the decrease of neurotransmitters in the brain. Funding Sources Ajinomoto Co., Inc.


2009 ◽  
Vol 4 (1) ◽  
pp. 1934578X0900400 ◽  
Author(s):  
Shio Murakami ◽  
Mariko Matsuura ◽  
Tadaaki Satou ◽  
Shinichiro Hayashi ◽  
Kazuo Koike

In phytotherapy, the essential oil from the leaves of Alpinia zerumbet ( Alpinia speciosa K. Schum.) (EOAZ) is used for neuropsychiatric symptoms, such as depression, stress and anxiety, and chronic problems that are associated with reproductive hormone imbalances in women. The chemical composition of EOAZ was analyzed by GC/MS, and the EOAZ properties inducing behavioral alterations in mice were examined by behavioral observations (BO) and an elevated plus-maze task (EPM), widely used as a method for assessing anxiolytic-like behaviors. Five major compounds, p-cymene (28.0 ± 5.0%), 1,8-cineole (17.9 ± 4.2%), terpinen-4-ol (11.9 ± 6.3%), limonene (6.3 ± 2.2%), and camphor (5.2 ± 2.1%) were identified by retention indices, mass spectra and comparison with standards. Inhalational administration of EOAZ (8.7 ppm) induced unique jumping behaviors in mice. To further investigate the behavioral regulatory mechanisms of EOAZ, we administered an intraperitoneal injection of either 10 mg/kg 5-HTP or 10 mg/kg fluoxetine prior to the EOAZ inhalations. By 5-HTP or fluoxetine pretreatments, the jumping frequencies were significantly decreased. In EPM, EOAZ (0.087 and 8.7 ppm) obviously showed the anxiolytic-like activity in mice.


Author(s):  
Ismail O. Ishola ◽  
Olufunsho Awodele ◽  
Chinedum O. Eluogu

Abstract:: HeMI (12.5–100 mg/kg, p.o.) was administered 1 h before subjecting the animal to the forced swim test (FST), tail suspension test (TST) and elevated plus maze tests (EPM).: HeMI (12.5–100 mg/kg, p.o.) treatment produced significant reduction in immobility time [F(6.56)=8.35, p<0.001], [F(6,56)=7.55, p<0.001] in the FST and TST, respectively. Moreover, co-administration of sub-therapeutic doses of imipramine or fluoxetine with HeMI (3.125 mg/kg) elicited significant reduction in time spent immobile in the FST. However, pretreatment of mice with parachlorophenylalanine, metergoline, yohimbine or sulpiride abolished the antidepressant-like effect elicited by HeMI. In the EPM, HeMI produced significant [F(5,42)=8.91, p<0.001] increase in open arms exploration by 75.55 % and this effect was blocked by pretreatment of mice with flumazenil or metergoline.: Findings from this study showed antidepressant-like effect of


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