Glycine/NMDA Receptor Pathway Mediates the Rapid-onset Antidepressant Effect of Alkaloids From Trichilia Monadelpha

Kennedy Kwami Edem Kukuia; Jeffrey Amoako Mensah; Patrick Amoateng; Dorcas Osei-Safo; Awo Efua Koomson; Joseph Torbi; Donatus Wewura Adongo; Elvis Ofori Ameyaw; Inemesit Okon Ben; Seth Kwabena Amponsah; Kwasi Agyei Bugyei; Isaac Julius Asiedu-Gyekye

doi:10.32598/bcn.12.3.2838.1

Glycine/NMDA Receptor Pathway Mediates the Rapid-onset Antidepressant Effect of Alkaloids From Trichilia Monadelpha

Basic Clin Neurosci. 2021 May-Jun;12(3):395-408. doi: 10.32598/bcn.12.3.2838.1. Epub 2021 May 1.

Affiliations

¹ Department of Medical Pharmacology, University of Ghana Medical School, College of Health Sciences, University of Ghana, Korle Bu-Accra, Ghana.
² Department of Pharmacology and Toxicology, College of Pharmacy, University of Utah, Salt Lake City, UT, U.S. A.
³ Department of Pharmacology and Toxicology, School of Pharmacy, College of Health Sciences, University of Ghana, Legon-Accra, Ghana.
⁴ Department of Chemistry, School of Physical and Mathematical Sciences, College of Basic and Applied Sciences, University of Ghana, Legon-Accra, Ghana.
⁵ Department of Pharmacology and Toxicology, School of Pharmacy, University of Health and Allied Sciences, Ho, Ghana.
⁶ Department of Pharmacology, School of Pharmacy and Pharmaceutical Sciences, University of Cape Coast, Cape Coast, Ghana.

Abstract

Introduction: Major depressive disorder is often associated with suicidal tendencies, and this condition accentuates the need for rapid-acting antidepressants. We previously reported that Alkaloids (ALK) from Trichilia monadelpha possess antidepressant action in acute animal models of depression and that this effect is mediated through the monoamine and L-arginine-NO-cGMP pathways. This study investigated the possible rapid-onset antidepressant effect of ALK from T. monadelpha and its connection with the glycine/NMDA receptor pathway.

Methods: The onset of ALK action from T. monadelpha was evaluated using the Open Space Swim Test (OSST), a chronic model of depression. The modified forced swimming and tail suspension tests were used to assess the effect of the ALK on the glycine/NMDA receptor pathway. The Instutute of Cancer Research (ICR) mice were treated with either ALK (30-300 mg/kg, orally [PO]), imipramine (3-30 mg/kg, PO), fluoxetine (3-30 mg/kg, PO), or saline. To identify the role of glycine/NMDA receptor pathway in the effect of ALK, we pretreated mice with a partial agonist of the glycine/NMDA receptor, D-cycloserine (2.5 mg/kg, intraperitoneally [IP]), and an agonist of glycine/NMDA receptor, D-serine (600 mg/kg, IP), before ALK administration.

Results: ALK reversed immobility in mice after the second day of drug treatment in the OSST. In contrast, there was a delay in the effects induced by fluoxetine and imipramine. ALK also increased mean swimming and climbing scores in mice. ALK was more efficacious than imipramine and fluoxetine in reducing immobility and increasing distance traveled. It is noteworthy that ALK was less potent than fluoxetine and imipramine. D-cycloserine potentiated mobility observed in the ALK- and fluoxetine-treated mice. In contrast, D-serine decreased mobility in the ALK-treated mice.

Conclusion: The study results suggest that ALK from T. monadelpha exhibits rapid antidepressant action in mice, and the glycine/NMDA receptor pathway possibly mediates the observed effect.

Keywords: Alkaloids; Glycine/NMDA receptor; Open space swim test; Rapid-acting antidepressant; Trichilia.