Ascorbic acid improves extrapyramidal syndromes and corpus striatal degeneration induced by dopamine-2 receptor inhibition in Wistar rats

Sirajo U. Mujittapha; Murtala Kauthar; Ishola O. Azeez; John C. Oyem

doi:10.1515/dmpt-2020-0137

Article

Ascorbic acid improves extrapyramidal syndromes and corpus striatal degeneration induced by dopamine-2 receptor inhibition in Wistar rats

Sirajo U. Mujittapha , Murtala Kauthar , Ishola O. Azeez and John C. Oyem

Published/Copyright: November 2, 2020

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From the journal Drug Metabolism and Personalized Therapy Volume 36 Issue 1

Abstract

Objectives

The prolonged uses of fourth-generation antipsychotics have been implicated in inducing extrapyramidal syndromes characterized by the motor deficit. This was attributed to the loss of dopamine-2 receptor (D2R) signaling. However, ascorbic acid (SVCT2R stimulation) in the brain is proposed to modulate D2R activity. We, therefore, investigated the beneficial roles of ascorbic acid in improving the extrapyramidal symptoms seen in D2R loss.

Methods

Twenty adult male Wistar rats of average weight 200 g were distributed randomly into four groups. The control (NS) received normal saline for 28 days, Untreated D2R inhibition group (−D2R) received normal saline for seven days and then subsequently received chlorpromazine for 21 days, D2R inhibition group treated with ascorbic acid (−D2R+SVCT2R) received chlorpromazine for 21 days and was subsequently treated with ascorbate for seven days while the withdrawal group (WG) received chlorpromazine for 21 days and subsequently received normal saline for seven days. Motor deficits were assessed using a rotarod and cylinder test. The corpus striatum was harvested, processed, and stained using H&E and Nissl stains. Cellular density was analyzed using Image J software 1.8.0.

Results

Motor deficit was observed in −D2R animals administered chlorpromazine with less improvement in WG compared to control (p<0.05) in both rotarod and cylinder test. Ascorbic acid (SVCT2R stimulation) significantly (p<0.001) improved the latency of fall and climbing attempts observed in −D2R animals. The density of basophilic trigoid bodies was significantly (p<0.001) restored in −D2R+SVCT2R group, suggesting recovery of neural activity in the corpus striatum. Moreover, the hallmarks of neuronal degeneration were less expressed in the ascorbic acid treatment groups.

Conclusions

Ascorbic acid putatively ameliorates extrapyramidal symptoms observed in D2R blockage by chlorpromazine in Wistar rats.

Keywords: ascorbic acid; chlorpromazine; corpus striatum; extrapyramidal syndromes

Corresponding author: Sirajo U. Mujittapha MSc, Department of Anatomy, Faculty of Basic Health Sciences, Bayero University, PMB 3011, Kano, Nigeria, Phone: +2348101682449, E-mail: mujittaphasurajo@gmail.com

Acknowledgments

We wish to acknowledge the support of Malam Yakubu, the caretaker of the animal house for his support in animal handling and behavioural studies, a huge thanks to Mr. James, a medical laboratory scientist for his support in reagent preparation. We cannot do without appreciating the management and members of staff of the Department of Human Anatomy, Bayero University Kano, Ahmadu Bello University, Zaria, and Afe Babalola University Ado-Ekiti, Nigeria.

Research funding: None declared.
Author contributions: Sirajo Mujittapha Umar and Kauthar Murtala designed the study and compiled report and data. Ishola Olakunle Azeez redesigned and interpreted all data. John Chukwuma Oyem revised the manuscript critically for important intellectual content. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: Authors state no conflict of interest.
Ethical approval: All animal handling was in line with the National Health Institute (NIH) and Institutional Animal Care and Use Committee (IACUC) guidelines and Bayero University Kano (BUK) Animal handling guidelines with Ref: BUK/ANA/18.

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Received: 2020-07-21

Accepted: 2020-08-24

Published Online: 2020-11-02

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Articles in the same Issue

https://doi.org/10.1515/dmpt-2020-0137

Keywords for this article

ascorbic acid; chlorpromazine; corpus striatum; extrapyramidal syndromes