Acth-induced model of depression resistant to tricyclic antidepressants: Neuroendocrine and behavioral changes and influence of long-term magnesium administration

Autor: Nela Puškaš, Svetlana Ignjatović, Duško Mirković, Dušanka Stanić, Vesna Pešić, Bojan Batinić, Jelena Petrović, Milica Labudovic-Borovic, Zorica Bulat
Rok vydání: 2018
Předmět:
0301 basic medicine
Male
medicine.medical_specialty
Hypothalamo-Hypophyseal System
Time Factors
Neurogenesis
Drug Resistance
Pituitary-Adrenal System
Adrenocorticotropic hormone
Major depressive disorder
Antidepressive Agents
Tricyclic
Treatment resistant depression
03 medical and health sciences
Behavioral Neuroscience
chemistry.chemical_compound
Glutamatergic
0302 clinical medicine
Endocrinology
Adrenocorticotropic Hormone
Corticosterone
Internal medicine
medicine
Animals
Magnesium
Treatment Failure
Rats
Wistar
chemistry.chemical_classification
Behavior
Animal
Endocrine and Autonomic Systems
business.industry
Depression
medicine.disease
Neurosecretory Systems
3. Good health
Rats
Disease Models
Animal
030104 developmental biology
Monoamine neurotransmitter
chemistry
Serotonin
business
Treatment-resistant depression
030217 neurology & neurosurgery
Tricyclic
Zdroj: Hormones and Behavior
Popis: Magnesium (Mg), is not only a modulator of the glutamatergic NMDA receptors' affinity, it also prevents HPA axis hyperactivity, thus possibly being implicated in neurobiological features of mood disorders. Further uncovering of molecular mechanisms underlying magnesium's proposed effects is needed due to the recent shift in research of treatment resistant depression (TRD) towards glutamatergic pathways. Here, we applied Mg via drinking water for 28 days (50 mg/kg/day), in ACTH-treated rats, an established animal model of depression resistant to tricyclic antidepressants. Using this model in male rats we measured (1) changes in hippocampal neurogenesis and behavioral alterations, (2) adrenal hormones response to acute stress challenge and (3) levels of biometals involved in regulation of monoamines turnover in rat prefrontal cortex. Our results support beneficial behavioral impact of Mg in TRD model together with increased hippocampal neurogenesis and BDNF expression. Furthermore, Mg prevented ACTH-induced disruption in HPA axis function, by normalizing the levels of plasma ACTH, corticosterone and interleukin-6, and by increasing the peripheral release of adrenaline, noradrenaline and serotonin after the acute stress challenge. Finally, the influence on copper/zinc ratio suggested probable magnesium's involvement in monoamine turnover in PFC. Our findings provide further insights into the possible pathways implicated in the behavioral modulation effects of Mg, as well as its central and peripheral effects in ACTH-induced TRD model. Thus, further investigation of molecular signaling related to the glutamatergic transmission and role of Mg, could reveal prospects to novel treatment strategies that could be of particular importance for patients suffering from TRD.
Databáze: OpenAIRE
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