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Inadequate dietary magnesium (Mg) intake is a growing public health concern. Mg is critical for diverse metabolic processes including energy production, macromolecule biosynthesis, and electrolyte homeostasis. Inadequate free Mg2+ ion concentration ([Mg2+]) in the brain is associated with several neurological and behavioral disorders. Elevating [Mg2+]in the brain using oral Mg supplementation has proven to be challenging due to the tight regulation of Mg2+ transport to the brain. This study explored the effect of short-term moderate reduction in dietary Mg intake (87% of normal Mg diet for 30 days) on [Mg2+] in the cerebrospinal fluid (CSF) ([Mg2+]CSF) and red blood cells (RBCs) ([Mg2+]RBC) in adult male rats. In addition, we investigated the effectiveness of magnesium-rich blend of Swiss chard and buckwheat extracts (SC/BW extract) in increasing brain [Mg2+] compared to various Mg salts commonly used as dietary supplements. Animals were assigned to either normal or low Mg diet for 30 - 45 days. Following this, animals maintained on low Mg diet were supplemented with various Mg compounds. [Mg2+]CSF and [Mg2+]RBC were measured at baseline and following Mg administration. Anxiety-like behavior and cognitive function were also evaluated. The present study showed that a short-term and moderate reduction in Mg dietary intake results in a significant decline in [Mg2+]CSF and [Mg2+]RBC and the emergence of anxiety-like behavior in comparison to animals maintained on normal Mg diet. Supplementation with SC/BW extract significantly elevated [Mg2+]CSF and improved animal performance in the novel object recognition test in comparison with animals maintained on reduced Mg intake and supplemented with various Mg compounds. These observations indicate that brain [Mg2+] is more sensitive to a short-term and moderate reduction in Mg dietary intake than previously thought and emphasizes the importance of dietary Mg in replenishing brain Mg2+ reserves. [ABSTRACT FROM AUTHOR]

Ketamine is noted for its rapid onset antidepressant response and effectiveness in patients with treatment resistant depression. While most research has focused on glutamatergic mechanisms, recent studies show that antidepressant-like effects in rodents are dependent upon the serotonergic (5-HT) system and suggest a potential contribution of the 5-HT 1B receptor. In this study we utilized CP-94253 to examine whether 5-HT 1B receptor agonism produces rapid and sustained antidepressant-like effects, focusing on rodent models and treatment approaches commonly used to demonstrate the differentiated response to ketamine. We first confirmed that CP-94253 is a potent 5-HT 1B agonist in vitro and that CP-94253 occupies brain 5-HT 1B receptors at the doses tested. CP-94253 reduced immobility in the mouse forced swim test (FST) and exhibited a prominent antidepressant signature in the mouse-behavior phenotyping platform SmartCube®. When examined 24 h after acute treatment, CP-94253 reduced FST immobility in both naïve rats and in rats receiving chronic interferon alpha treatment. Ex vivo hippocampal long-term potentiation was also enhanced in naïve rats receiving acute CP-94253 treatment, 24 h prior to the recordings. In mice exposed to chronic social defeat stress, antidepressant-like effects in the tail suspension and sucrose preference tests were seen 1 h and 24 h after acute treatment, respectively. Finally, whole brain c-fos imaging in mice showed that CP-94253 modulates neuronal activity in discrete brain regions including the lateral habenula circuit implicated in depression and the ketamine treatment response. Collectively these results support the further investigation of 5-HT 1B agonism as a novel treatment approach for major depressive disorder., Competing Interests: Declaration of competing interest At the time these studies were conducted the authors were employees of the following companies: Sumitomo Pharma America Inc. (Erin Clark, Lien Wang, Kenneth Koblan, Nina Dedic, Linda Bristow); Psychogenics Inc. (Taleen Hanania, Karla Kretschmannova); Ulysses Neuroscience Ltd. (Massimiliano Bianchi); Sygnature Discovery (Elizabeth Jagger); Gubra ApS (Yasir Gallero-Salas); HD Biosciences Company Ltd. (Tingting Hu, Fugang Li)., (Copyright © 2024 Elsevier Inc. All rights reserved.)