QCM-4, a serotonergic type 3 receptor modulator attenuates depression co-morbid with obesity in mice: An approach based on behavioral and biochemical investigations

Kurhe, Yeshwant; Mahesh, Radhakrishnan; Gupta, Deepali; Devadoss, Thangaraj

doi:10.1016/j.ejphar.2014.06.020

Cited by 16 publications

(4 citation statements)

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“…The results obtained in this study are consistent with those reported for A2AR antagonists that reverted the anhedonia-like (loss of interest or pleasure) condition in OBX rats, which is the main depression diagnostic criteria (DSM-V) and is consistent with previous studies (Kaster et al, 2015) and escitalopram treatment (Kurhe, Mahesh, Gupta, & Devadoss, 2014). The significant increase in sucrose preference of the OBX + ZM group may be due to the fact that blocking A2ARs could improve motivational dysfunction through regulation of the mesolimbic dopaminergic circuit involved in effort-related decision making (Yohn et al, 2015).…”

Section: Discussionsupporting

confidence: 93%

Behavioral changes induced through adenosine A2A receptor ligands in a rat depression model induced by olfactory bulbectomy

et al. 2018

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BackgroundMajor depressive disorders are characterized by their severity and long‐lasting symptoms, which make such disorders highly disabling illnesses. Unfortunately, 50% of major depressive patients experience relapses, perhaps partly because drug research has been performed only in animal models that screen for antidepressant drugs that appear to only ameliorate acute depression symptoms. The bilateral olfactory bulbectomy (OBX) animal model presents the advantage of mimicking the symptoms of chronic depression by means of brain surgery. Adenosine purinergic receptors A2A (A2AR) have been the target of interest in the field of psychiatric diseases. This study aimed to show which A2A receptor ligands exert antidepressive‐like effects in the OBX rat model.MethodsForty Sprague‐Dawley male rats were divided into four groups: control, OBX + vehicle, OBX + ZM 241385, and OBX + adenosine groups. Pharmacological treatment was administered for 14 days, and the rats were examined via the forced swim test (FST), open field test (OFT), and sucrose preference test (SPT).ResultsThe OBX + ZM 241385 group exhibited decreased immobility time in the FST, decreased isolation time in the OFT, and reversed anhedonia behavior in the SPT compared to the vehicle group. However, no significant differences for adenosine treatment were found.Conclusions ZM 241385 administration (2 mg/kg i.p.) restored behavioral changes associated with OBX‐induced depression.

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Section: Discussionsupporting

confidence: 93%

Behavioral changes induced through adenosine A2A receptor ligands in a rat depression model induced by olfactory bulbectomy

et al. 2018

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“…The connection between obesity and behavioral deficits is further supported by evidence showing that some anti-obesity therapies exert anxiolytic effects. Thus, several drugs used to treat obesity have attenuated behavioral alterations in mice, such as sibutramine (Santos et al, 2014 ), duloxetine (Chudasama and Bhatt, 2009 ), pioglitazone (Kurhe and Mahesh, 2016 ), celecoxib (Kurhe et al, 2014a ), ondansetron (Kurhe and Mahesh, 2015 ), 3-methoxy-N-p-tolylquinoxalin-2-carboxamide (QCM-4) (Kurhe et al, 2014b , 2015 ), GPR120 agonist (Auguste et al, 2016 ). These findings suggest that obesity and emotional disorders, such as anxiety and depression, could share a common base.…”

Section: Effects Of Obesity On Cognitive Functions and Moodmentioning

confidence: 99%

Interplay Between the Gut-Brain Axis, Obesity and Cognitive Function

et al. 2018

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Obesity continues to be one of the major public health problems due to its high prevalence and co-morbidities. Common co-morbidities not only include cardiometabolic disorders but also mood and cognitive disorders. Obese subjects often show deficits in memory, learning and executive functions compared to normal weight subjects. Epidemiological studies also indicate that obesity is associated with a higher risk of developing depression and anxiety, and vice versa. These associations between pathologies that presumably have different etiologies suggest shared pathological mechanisms. Gut microbiota is a mediating factor between the environmental pressures (e.g., diet, lifestyle) and host physiology, and its alteration could partly explain the cross-link between those pathologies. Westernized dietary patterns are known to be a major cause of the obesity epidemic, which also promotes a dysbiotic drift in the gut microbiota; this, in turn, seems to contribute to obesity-related complications. Experimental studies in animal models and, to a lesser extent, in humans suggest that the obesity-associated microbiota may contribute to the endocrine, neurochemical and inflammatory alterations underlying obesity and its comorbidities. These include dysregulation of the HPA-axis with overproduction of glucocorticoids, alterations in levels of neuroactive metabolites (e.g., neurotransmitters, short-chain fatty acids) and activation of a pro-inflammatory milieu that can cause neuro-inflammation. This review updates current knowledge about the role and mode of action of the gut microbiota in the cross-link between energy metabolism, mood and cognitive function.

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“…Ondansetron, a 5-HT 3 receptor antagonist is currently being used for the treatment of post-operative nausea and vomiting (PONV) and chemotherapy induced nausea and vomiting (CINV) (Tramer et al, 1997;Parker et al, 2001;Cohen, 2007). Several preclinical studies have demonstrated the antidepressant and anxiolytic effects of serotonergic type 3 (5-HT 3 ) receptor antagonists, such as ondansetron (Ramamoorthy et al, 2008;Rajkumar and Mahesh, 2010;Roychoudhury and Kulkarni, 1997), 3-methoxy-N-p-tolylquinoxalin-2-carboxamide (QCM-4) (Kurhe et al, 2014a) and (4-phenylpiperazin-1-yl) (quinoxalin-2-yl) methanone (4a) (Kurhe et al, 2015). Earlier we reported the antidepressant activity of ondansetron based on the behavioral tests in obese mice subjected to chronic stress (Kurhe et al, 2014b).…”

Section: Introductionmentioning

confidence: 99%

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

Kurhe

Mahesh

2015

Pharmacology Biochemistry and Behavior

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QCM-4, a serotonergic type 3 receptor modulator attenuates depression co-morbid with obesity in mice: An approach based on behavioral and biochemical investigations

Cited by 16 publications

References 64 publications

Behavioral changes induced through adenosine A2A receptor ligands in a rat depression model induced by olfactory bulbectomy

Behavioral changes induced through adenosine A2A receptor ligands in a rat depression model induced by olfactory bulbectomy

Interplay Between the Gut-Brain Axis, Obesity and Cognitive Function

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

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