Glycine/NMDA Receptor Pathway Mediates the Rapid-onset Antidepressant Effect of Alkaloids From Trichilia Monadelpha
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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Iran University of Medical Sciences
2021-05-01
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| Series: | Basic and Clinical Neuroscience |
| Subjects: | |
| Online Access: | http://bcn.iums.ac.ir/article-1-1907-en.html |
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| author | 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 |
| author_facet | 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 |
| author_sort | Kennedy Kwami Edem Kukuia |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-07T17:26:04Z |
| format | Article |
| id | doaj.art-3af59a48d77b4c128724ee7fe2ad9c94 |
| institution | Directory Open Access Journal |
| issn | 2008-126X 2228-7442 |
| language | English |
| last_indexed | 2024-03-07T17:26:04Z |
| publishDate | 2021-05-01 |
| publisher | Iran University of Medical Sciences |
| record_format | Article |
| series | Basic and Clinical Neuroscience |
| spelling | doaj.art-3af59a48d77b4c128724ee7fe2ad9c942024-03-02T19:02:40ZengIran University of Medical SciencesBasic and Clinical Neuroscience2008-126X2228-74422021-05-01123395408Glycine/NMDA Receptor Pathway Mediates the Rapid-onset Antidepressant Effect of Alkaloids From Trichilia MonadelphaKennedy Kwami Edem Kukuia0Jeffrey Amoako Mensah1Patrick Amoateng2Dorcas Osei-Safo3Awo Efua Koomson4Joseph Torbi5Donatus Wewura Adongo6Elvis Ofori Ameyaw7Inemesit Okon Ben8Seth Kwabena Amponsah9Kwasi Agyei Bugyei10Isaac Julius Asiedu-Gyekye11 Department of Medical Pharmacology, University of Ghana Medical School, College of Health Sciences, University of Ghana, Korle Bu-Accra, Ghana. Department of Pharmacology and Toxicology, College of Pharmacy, University of Utah, Salt Lake City, UT, U.S. A. Department of Pharmacology and Toxicology, School of Pharmacy, College of Health Sciences, University of Ghana, Legon-Accra, Ghana. Department of Chemistry, School of Physical and Mathematical Sciences, College of Basic and Applied Sciences, University of Ghana, Legon-Accra, Ghana. Department of Pharmacology and Toxicology, School of Pharmacy, College of Health Sciences, University of Ghana, Legon-Accra, Ghana. Department of Pharmacology and Toxicology, School of Pharmacy, College of Health Sciences, University of Ghana, Legon-Accra, Ghana. Department of Pharmacology and Toxicology, School of Pharmacy, University of Health and Allied Sciences, Ho, Ghana. Department of Pharmacology, School of Pharmacy and Pharmaceutical Sciences, University of Cape Coast, Cape Coast, Ghana. Department of Pharmacology and Toxicology, School of Pharmacy, University of Health and Allied Sciences, Ho, Ghana. Department of Medical Pharmacology, University of Ghana Medical School, College of Health Sciences, University of Ghana, Korle Bu-Accra, Ghana. Department of Medical Pharmacology, University of Ghana Medical School, College of Health Sciences, University of Ghana, Korle Bu-Accra, Ghana. Department of Pharmacology and Toxicology, School of Pharmacy, College of Health Sciences, University of Ghana, Legon-Accra, Ghana. 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.http://bcn.iums.ac.ir/article-1-1907-en.htmlglycine/nmda receptoropen space swim testrapid-acting antidepressanttrichiliaalkaloids |
| spellingShingle | 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 Glycine/NMDA Receptor Pathway Mediates the Rapid-onset Antidepressant Effect of Alkaloids From Trichilia Monadelpha Basic and Clinical Neuroscience glycine/nmda receptor open space swim test rapid-acting antidepressant trichilia alkaloids |
| title | Glycine/NMDA Receptor Pathway Mediates the Rapid-onset Antidepressant Effect of Alkaloids From Trichilia Monadelpha |
| title_full | Glycine/NMDA Receptor Pathway Mediates the Rapid-onset Antidepressant Effect of Alkaloids From Trichilia Monadelpha |
| title_fullStr | Glycine/NMDA Receptor Pathway Mediates the Rapid-onset Antidepressant Effect of Alkaloids From Trichilia Monadelpha |
| title_full_unstemmed | Glycine/NMDA Receptor Pathway Mediates the Rapid-onset Antidepressant Effect of Alkaloids From Trichilia Monadelpha |
| title_short | Glycine/NMDA Receptor Pathway Mediates the Rapid-onset Antidepressant Effect of Alkaloids From Trichilia Monadelpha |
| title_sort | glycine nmda receptor pathway mediates the rapid onset antidepressant effect of alkaloids from trichilia monadelpha |
| topic | glycine/nmda receptor open space swim test rapid-acting antidepressant trichilia alkaloids |
| url | http://bcn.iums.ac.ir/article-1-1907-en.html |
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