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

• Published in: Basic and clinical neuroscience Vol. 12; no. 3; pp. 395 - 408
• Main Authors: Kukuia, Kennedy Kwami Edem, Mensah, Jeffrey Amoako, Amoateng, Patrick, Osei-Safo, Dorcas, Koomson, Awo Efua, Torbi, Joseph, Adongo, Donatus Wewura, Ameyaw, Elvis Ofori, Ben, Inemesit Okon, Amponsah, Seth Kwabena, Bugyei, Kwasi Agyei, Asiedu-Gyekye, Isaac Julius
• Format: Journal Article
• Language: English
• Published: Iran Negah Scientific Publisher 01.05.2021; Iranian Neuroscience Society; Iran University of Medical Sciences
• Subjects: Agonists; Alkaloids; Animal models; Antidepressants; Arginine; Cycloserine; D-Serine; Fluoxetine; Glutamic acid receptors (ionotropic); Glycine; glycine/nmda receptor; Imipramine; Mental depression; Mobility; N-Methyl-D-aspartic acid receptors; open space swim test; rapid-acting antidepressant; Research Paper; Trichilia; Rapid-acting antidepressant; Trichilia; Alkaloids; Open space swim test; Glycine/NMDA receptor
• ISSN: 2008-126X; 2228-7442; 2228-7442
• DOI: 10.32598/bcn.12.3.2838.1

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 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 and its connection with the glycine/NMDA receptor pathway. The onset of ALK action from 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. 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. The study results suggest that ALK from exhibits rapid antidepressant action in mice, and the glycine/NMDA receptor pathway possibly mediates the observed effect.