Antidepressant-like activity of magnesium in the olfactory bulbectomy model is associated with the AMPA/BDNF pathway

Rationale Numerous studies suggest agents that act on glutamatergic transmission as potential antidepressants. Preclinical and clinical evidence suggests that magnesium, an N -methyl- d -aspartate receptor blocker, may be useful in the treatment of depression. Objective The aim of this study was to...

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Vydáno v:	Psychopharmacology Ročník 232; číslo 2; s. 355 - 367
Hlavní autoři:	Pochwat, Bartlomiej, Sowa-Kucma, Magdalena, Kotarska, Katarzyna, Misztak, Paulina, Nowak, Gabriel, Szewczyk, Bernadeta
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Berlin/Heidelberg Springer Berlin Heidelberg 01.01.2015 Springer Springer Nature B.V
Témata:	alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid - metabolism Amitriptyline - pharmacology Analysis Animals Antidepressants Antidepressive Agents - pharmacology Biomedical and Life Sciences Biomedicine Brain Brain - drug effects Brain - metabolism Brain-derived neurotrophic factor Brain-Derived Neurotrophic Factor - metabolism Care and treatment Depression (Mood disorder) Depression - drug therapy Depression - metabolism Diagnosis Disease Models, Animal Dosage and administration Magnesium Magnesium - pharmacology Male Mental depression Metabolic Networks and Pathways - drug effects MicroRNAs N-methyl-D-aspartate Neurosciences Olfactory Bulb - surgery Original Investigation Pharmacology/Toxicology Psychiatry Psychopharmacology Rats Rats, Sprague-Dawley Receptors, AMPA - metabolism Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors Receptors, N-Methyl-D-Aspartate - metabolism Risk factors RNA Rodents Smell Poland AMPA BDNF NMDA Glutamatergic system Depression Magnesium Olfactory bulbectomy
ISSN:	0033-3158, 1432-2072, 1432-2072
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Shrnutí:	Rationale Numerous studies suggest agents that act on glutamatergic transmission as potential antidepressants. Preclinical and clinical evidence suggests that magnesium, an N -methyl- d -aspartate receptor blocker, may be useful in the treatment of depression. Objective The aim of this study was to investigate the effects of magnesium on behavior; protein levels of GluN2A, GluN2B [ N -methyl- d -aspartate receptor (NMDAR) subunits], GluA1 [α-amino-3-hydroxy-5 methyl-4-isoxazolepropionic acid (AMPA) subunit], phospho-Ser-831-GluA1 (P-S831), phospho-Ser-845-GluA1 (P-S845), and brain-derived neurotrophic factor (BDNF); and messenger RNA (mRNA) levels of GluN2A and GluN2B in different brain areas in the olfactory bulbectomy (OB) model of depression in rats. Methods Magnesium was administered once daily for 14 days at three doses (10, 15, and 20 mg/kg, intraperitoneal) to sham and OB rats. Following treatment, open field and passive avoidance tests were performed in the sham and OB rats. After 24 h, the hippocampus, the prefrontal cortex (PFC), and the amygdala of rats treated with the most active dose (15 mg/kg) were harvested, and the protein and mRNA levels were determined. Results Chronic administration of magnesium (15 and 20 mg/kg) reduced the number of trials required to learn passive avoidance and reduced the OB-induced hyperactivity. OB increased the P-S845 level in the hippocampus, which was reduced by magnesium treatment. Magnesium significantly increased the levels of BDNF, GluN2B, P-S831, and P-S845 protein (and mRNA) primarily in the PFC and the hippocampus in OB rats. Conclusion For the first time, the present results demonstrate the antidepressant-like activity of magnesium in the OB animal model of depression and indicate the potential involvement of the AMPA/BDNF pathway in this activity.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	0033-3158 1432-2072 1432-2072
DOI:	10.1007/s00213-014-3671-6