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

• Published in: Drug metabolism and drug interactions Vol. 36; no. 1; pp. 47 - 52
• Main Authors: Mujittapha, Sirajo U., Kauthar, Murtala, Azeez, Ishola O., Oyem, John C.
• Format: Journal Article
• Language: English
• Published: Berlin De Gruyter 30.03.2021; Walter de Gruyter GmbH
• Subjects: Acids; ascorbic acid; chlorpromazine; corpus striatum; Dopamine; extrapyramidal syndromes; Rodents; Vitamin C
• ISSN: 0792-5077; 2191-0162
• DOI: 10.1515/dmpt-2020-0137

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.