Glycine/NMDA Receptor Pathway Mediates the Rapid-onset Antidepressant Effect of Alkaloids From Trichilia Monadelpha
Authors:   Department of Medical Pharmacology, University of Ghana Medical School, College of Health Sciences, University of Ghana, Korle Bu-Accra, Ghana., Edem Kukuia Kennedy Kwami , Amoako Mensah Jeffrey ,   Department of Pharmacology and Toxicology, College of Pharmacy, University of Utah, Salt Lake City, UT, U.S. A., Amoateng Patrick ,   Department of Pharmacology and Toxicology, School of Pharmacy, College of Health Sciences, University of Ghana, Legon-Accra, Ghana., Osei-Safo Dorcas ,   Department of Chemistry, School of Physical and Mathematical Sciences, College of Basic and Applied Sciences, University of Ghana, Legon-Accra, Ghana., Efua Koomson Awo ,   Department of Pharmacology and Toxicology, School of Pharmacy, College of Health Sciences, University of Ghana, Legon-Accra, Ghana., Torbi Joseph ,   Department of Pharmacology and Toxicology, School of Pharmacy, College of Health Sciences, University of Ghana, Legon-Accra, Ghana., Wewura Adongo Donatus ,   Department of Pharmacology and Toxicology, School of Pharmacy, University of Health and Allied Sciences, Ho, Ghana., Ofori Ameyaw Elvis ,   Department of Pharmacology, School of Pharmacy and Pharmaceutical Sciences, University of Cape Coast, Cape Coast, Ghana., Okon Ben Inemesit ,   Department of Pharmacology and Toxicology, School of Pharmacy, University of Health and Allied Sciences, Ho, Ghana., Kwabena Amponsah Seth ,   Department of Medical Pharmacology, University of Ghana Medical School, College of Health Sciences, University of Ghana, Korle Bu-Accra, Ghana., Agyei Bugyei Kwasi ,   Department of Medical Pharmacology, University of Ghana Medical School, College of Health Sciences, University of Ghana, Korle Bu-Accra, Ghana., Asiedu-Gyekye Isaac Julius ,   Department of Pharmacology and Toxicology, School of Pharmacy, College of Health Sciences, University of Ghana, Legon-Accra, Ghana.
Published: August 2021

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.