Improved serotonergic neurotransmission by genistein pretreatment regulates symptoms of obsessive-compulsive disorder in streptozotocin-induced diabetic mice

Pradeep Phadnis; Purnima Dey Sarkar; Mithun Singh Rajput

doi:10.1515/jbcpp-2017-0155

Article

Improved serotonergic neurotransmission by genistein pretreatment regulates symptoms of obsessive-compulsive disorder in streptozotocin-induced diabetic mice

Pradeep Phadnis , Purnima Dey Sarkar and Mithun Singh Rajput

Published/Copyright: March 21, 2018

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From the journal Journal of Basic and Clinical Physiology and Pharmacology Volume 29 Issue 4

Abstract

Background

Initial evidences have shown that diabetes mellitus occurs concomitantly with obsessive-compulsive disorder (OCD) symptomatology. Serotonergic psychiatric therapy posits that serotonin is a central character in the management of OCD. Hence, it is worth investigating novel chemical entities affecting the serotonergic system for targeting OCD. An isoflavonoid phytoestrogen, genistein, has been recognized as of great pharmacological value especially for protecting neurodegeneration, depression (serotonin regulation), and diabetes. The effectiveness of genistein pretreatment on the symptoms of OCD in streptozotocin-induced diabetic mice is investigated in this study. We also evaluate the probable involvement of the serotonergic system.

Methods

Groups of diabetic mice were treated with genistein at the dose of 5.0 and 10.0 mg/kg (intraperitoneal, twice daily, 14 days), and symptoms of OCD were assessed by the marble-burying behavior, in comparison with the standard drug fluoxetine. Neurochemical assessment of the serotonergic ratio 5-hydroxyindole-3-methoxyphenylacetic acid/5-hydroxytryptamine (5-HIAA/5-HT) in the cortical region of the brain was performed using HPLC (high-pressure liquid chromatography).

Results

Chronic treatment with genistein significantly recovered [F(6, 35)=53.00, p<0.0001, R²=0.9008] the symptoms of OCD as assessed by marble burying behavior in normal and diabetic mice. Locomotor performance was not influenced by the diabetic condition or any associated treatment. The turnover of serotonin neurotransmission (5-HIAA/5-HT) was significantly boosted in the diabetic condition; genistein treatment dragged it [F(6, 35)=35.75, p<0.0001, R²=0.8597] toward the respective control.

Conclusions

Genistein supplementation might be a potential therapeutic line for the management and/or prevention of diabetes-associated OCD symptomatology.

Keywords: genistein; marble burying; obsessive-compulsive disorder; serotonin

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/jbcpp-2017-0155).

Received: 2017-09-12

Accepted: 2018-01-02

Published Online: 2018-03-21

Published in Print: 2018-07-26

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Supplementary material

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Keywords for this article

genistein; marble burying; obsessive-compulsive disorder; serotonin