Ondansetron attenuates co-morbid depression and anxiety associated with obesity by inhibiting the biochemical alterations and improving serotonergic neurotransmission

Kurhe, Yeshwant; Mahesh, Radhakrishnan

doi:10.1016/j.pbb.2015.07.004

Cited by 27 publications

(20 citation statements)

References 110 publications

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“…The reasons for these differences are not clear, but they may be related to the length of exposure of the animals to the high caloric diet, to diet composition and to the action of compensatory mechanisms [10, 56]. Thus, whereas in our experiments rats were exposed 24 weeks to the high-sucrose diet, in the case of Sharma and Fulton [14], Kurhe [16, 17] and Yamada et al [55] for 12, 14 and 16 weeks respectively, and in the work of Tannenbaum et al [51] rats were only exposed for 21 days.…”

Section: Discussionmentioning

confidence: 98%

“…Accordingly, whereas mice kept under a medium-term HFD (either 6, 12 or 14 weeks) developed an anxiogenic-like profile in different anxiety paradigms [14–17], rats eating a similar diet for a week show instead an anxiolytic-like behavior in the elevated-plus-maze (EPM) [18, 19]. In addition, no effects in anxiety were however found when mice were evaluated after a moderate-term (13 weeks) HFD in a triple anxiety test (open-field test (OFT) + EPM + light-dark box test (LDBT) [20].…”

Section: Introductionmentioning

confidence: 99%

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Increased anxiety-like behavior is associated with the metabolic syndrome in non-stressed rats

et al. 2017

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Metabolic syndrome (MS) is a cluster of signs that increases the risk to develop diabetes mellitus type 2 and cardiovascular disease. In the last years, a growing interest to study the relationship between MS and psychiatric disorders, such as depression and anxiety, has emerged obtaining conflicting results. Diet-induced MS rat models have only examined the effects of high-fat or mixed cafeteria diets to a limited extent. We explored whether an anxiety-like behavior was associated with MS in non-stressed rats chronically submitted to a high-sucrose diet (20% sucrose in drinking water) using three different anxiety paradigms: the shock-probe/burying test (SPBT), the elevated plus-maze (EPM) and the open-field test (OFT). Behaviorally, the high-sucrose diet group showed an increase in burying behavior in the SPBT. Also, these animals displayed both avoidance to explore the central part of the arena and a significant increase in freezing behavior in the OFT and lack of effects in the EPM. Also, high-sucrose diet group showed signs of an MS-like condition: significant increases in body weight and body mass index, abdominal obesity, hypertension, hyperglycemia, hyperinsulinemia, and dyslipidemia. Plasma leptin and resistin levels were also increased. No changes in plasma corticosterone levels were found. These results indicate that rats under a 24-weeks high-sucrose diet develop an MS associated with an anxiety-like behavior. Although the mechanisms underlying this behavioral outcome remain to be investigated, the role of leptin is emphasized.

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Increased anxiety-like behavior is associated with the metabolic syndrome in non-stressed rats

et al. 2017

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“…Dexamethasone and ondansetron were diluted with sterile water for injection and dosed on the day of chemotherapy administration and for 3 days post chemotherapy. Dose titrations were conducted for dexamethasone while ondansetron was dosed at the commonly reported dose of 1 mg/kg in mice [ 20 ].…”

Section: Methodsmentioning

confidence: 99%

A systematic investigation of the maximum tolerated dose of cytotoxic chemotherapy with and without supportive care in mice

et al. 2017

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BackgroundCytotoxic chemotherapeutics form the cornerstone of systemic treatment of many cancers. Patients are dosed at maximum tolerated dose (MTD), which is carefully determined in phase I studies. In contrast, in murine studies, dosages are often based on customary practice or small pilot studies, which often are not well documented. Consequently, research groups need to replicate experiments, resulting in an excess use of animals and highly variable dosages across the literature. In addition, while patients often receive supportive treatments in order to allow dose escalation, mice do not. These issues could affect experimental results and hence clinical translation.MethodsTo address this, we determined the single-dose MTD in BALB/c and C57BL/6 mice for a range of chemotherapeutics covering the canonical classes, with clinical score and weight as endpoints.ResultsWe found that there was some variation in MTDs between strains and the tolerability of repeated cycles of chemotherapy at MTD was drug-dependent. We also demonstrate that dexamethasone reduces chemotherapy-induced weight loss in mice.ConclusionThese data form a resource for future studies using chemotherapy in mice, increasing comparability between studies, reducing the number of mice needed for dose optimisation experiments and potentially improving translation to the clinic.Electronic supplementary materialThe online version of this article (10.1186/s12885-017-3677-7) contains supplementary material, which is available to authorized users.

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“…In CHD, research suggests that obese patients with myocardium are more susceptible to ischemia compared to nonobese people, with enhanced levels of ROS and ROS-producing enzymes (i.e., p47phox, xanthine oxidase) and reduced antioxidant activity (mitochondrial aldehyde dehydrogenase and heme oxygenase-1) [84]. In depression, obese mice fed with high-fat diet had severe depressive behaviors, which could be reversed by ondansetron treatment via restoration of brain prooxidant/antioxidant balance [85] and by allicin via activation of the Nrf2 pathway [86]. Apart from preclinical investigations, human studies have indicated that postpartum depression affects one in seven women, and obese women have an increased risk of depression through neurooxidation and neuronitrosation [87,88].…”

Section: Oxidative Stress and Risk Factorsmentioning

confidence: 99%

The Role of Oxidative Stress in Common Risk Factors and Mechanisms of Cardio-Cerebrovascular Ischemia and Depression

Lin

Wang

Yan

et al. 2019

Oxidative Medicine and Cellular Longevity

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The public health sector faces a huge challenge as a result of the high prevalence and burden of disability caused by ischemic cardio-cerebrovascular disease (CVD) and depression. Although studies have explored the underlying mechanisms and potential therapies to address conditions, there is no treatment breakthrough, especially for depression which is highly influenced by social stressors. However, accumulating evidence reveals that CVD and depression are correlated and share common risk factors, particularly obesity, diabetes, and hypertension. They also share common mechanisms, including oxidative stress (OS), inflammation and immune response, cell death signaling pathway, and microbiome-gut-brain axis. This review summarizes the relationship between ischemic CVD and depression and describes the interactions among common risk factors and mechanisms for these two diseases. In addition, we propose that OS mediates the crosstalk between these diseases. We also reveal the potential of antioxidants to ameliorate OS-related injuries.

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Ondansetron attenuates co-morbid depression and anxiety associated with obesity by inhibiting the biochemical alterations and improving serotonergic neurotransmission

Cited by 27 publications

References 110 publications

Increased anxiety-like behavior is associated with the metabolic syndrome in non-stressed rats

Increased anxiety-like behavior is associated with the metabolic syndrome in non-stressed rats

A systematic investigation of the maximum tolerated dose of cytotoxic chemotherapy with and without supportive care in mice

The Role of Oxidative Stress in Common Risk Factors and Mechanisms of Cardio-Cerebrovascular Ischemia and Depression

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