Metabotropic glutamate 2/3 receptor antagonists improve behavioral and prefrontal dopaminergic alterations in the chronic corticosterone-induced depression model in mice

Ago, Yukio; Yano, Koji; Araki, Ryoko; Hiramatsu, Naoki; Kita, Yuki; Kawasaki, Toshiyuki; Onoe, Hirotaka; Chaki, Shigeyuki; Nakazato, Atsuro; Hashimoto, Hitoshi; Baba, Akemichi; Takuma, Kazuhiro; Matsuda, Takehisa

doi:10.1016/j.neuropharm.2012.09.008

Cited by 84 publications

(50 citation statements)

References 64 publications

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“…This is believed to release energy stores to help the animal cope with the stressful stimulus and, in turn, this surplus energy is used to display the behavioral responses [33]. Nevertheless, persistent secretion of corticosterone during chronic stress induces further energy loss and structural changes in several regions of the brain, which are accompanied by impairment of some brain functions, such as learning and memory [1].…”

Section: Discussionmentioning

confidence: 99%

Defensive responses of Brandt's voles (Lasiopodomys brandtii) to chronic predatory stress

Hegab

Shang

et al. 2014

Physiology & Behavior

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Predator odors are non-intrusive natural stressors of high ethological relevance. The objective of this study was to investigate the processing of a chronic, life-threatening stimulus during repeated prolonged presentation to Brandt's voles. One hundred and twenty voles were tested by repeated presentation of cat feces in a defensive withdrawal apparatus. Voles exposed to feces for short periods showed more avoidance, more concealment in the hide box, less contact time with the odor source, more freezing behavior, less grooming, more jumping, and more vigilant rearing than did non-exposed voles, and those exposed for longer periods. Serum levels of adrenocorticotropic hormone and corticosterone increased significantly when animals were repeatedly exposed to cat feces for short periods. The behavioral and endocrine responses habituated during prolonged presentation of cat feces. ΔfosB mRNA expression level was highest in voles exposed to cat feces for 6 and 12 consecutive days, and subsequently declined in animals exposed to cat feces for 24 days. We therefore conclude that the behavioral and endocrine responses to repeated exposure to cat feces undergo a process of habituation, while ΔfosB changes in the medial hypothalamic region exhibit sensitization. We propose that habituation and sensitization are complementary rather than contradictory processes that occur in the same individual upon repeated presentation of the same stressor.

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Section: Discussionmentioning

confidence: 99%

Defensive responses of Brandt's voles (Lasiopodomys brandtii) to chronic predatory stress

Hegab

Shang

et al. 2014

Physiology & Behavior

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“…The FST was performed by a previously reported method, with some modification (Ago et al, 2013). Although immobility in the FST is a controversial measure of depressive-like behavior, it is a useful screen for compounds that are effective for the treatment of depression.…”

Section: Forced Swimming Testmentioning

confidence: 99%

The Antidepressant Effects of an mGlu2/3 Receptor Antagonist and Ketamine Require AMPA Receptor Stimulation in the mPFC and Subsequent Activation of the 5-HT Neurons in the DRN

Fukumoto

Iijima

Chaki

2015

Neuropsychopharmacol

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147

117

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We have reported the antidepressant effects of both metabotropic glutamate 2/3 (mGlu2/3) receptor antagonists and ketamine in several animal models, and proposed that serotonergic (5-HTergic) transmission is involved in these actions. Given that the projections from the medial prefrontal cortex (mPFC) to the dorsal raphe nucleus (DRN), where the majority of serotonin (5-HT) neurons exist, are reportedly involved in the antidepressant effects, in this study, we investigated using the forced swimming test (FST) of C57BL/6J male mice, the role of 5-HT neurons in the DRN regulated by the mPFC-DRN projections in the antidepressant effects of an mGlu2/3 receptor antagonist, LY341495, and ketamine. Following systemic administration/microinjection into the mPFC, both LY341495 and ketamine were found to exert antidepressant effects in the FST, and the effects were attenuated by depletion of 5-HT by treatment with an inhibitor of 5-HT synthesis, PCPA. The antidepressant effects of LY341495 and ketamine were also blocked by systemic administration/microinjection into the mPFC of an AMPA receptor antagonist, NBQX. Moreover, systemic administration/microinjection into the mPFC of LY341495 and ketamine significantly increased the c-Fos expression in the 5-HT neurons in the DRN, and the effect of systemic administration of these drugs on the neuronal c-Fos expression was attenuated by microinjection of NBQX into the mPFC. Our findings suggest that activation of 5-HT neurons in the DRN regulated by stimulation of the AMPA receptor in the mPFC may be involved in the antidepressant effects of an mGlu2/3 receptor antagonist and ketamine.

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“…Currently, it has been confi rmed that mGluR2/3 antagonists have antidepressant effects [65] that have many features in common with those of ketamine. This is because mGluR2/3 regulates glutamate release by negative feedback; hence, glutamate release in the synaptic cleft is largely enhanced after blocking mGluR2/3, and the increased glutamate further activates AMPARs and facilitates the activation of the downstream PI3K-AKT-mTOR pathway to exert antidepressant effects.…”

Section: The Abnormal Glutamate Receptors Hypothesis and Related New mentioning

confidence: 99%

New hypothesis and treatment targets of depression: an integrated view of key findings

2015

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Major depressive disorder (MDD) is a common and devastating psychiatric disorder characterized by persistent low mood, cognitive disorder, and impaired social function. Despite its complex mechanisms, increasing evidence has identified the involvement of neurotrophic factors, inflammatory cytokines, the hypothalamuspituitary-adrenal axis, and glutamate receptors in the pathophysiology of this illness. The present review synthesizes recent research achievements to defi ne the network between different hypotheses of MDD and to understand which part is most pivotal for its pathogenesis. By integrating MDD-related signal pathways, we highlight brain-derived neurotrophic factor (BDNF) dysfunction and increased apoptosis as the fi nal common cascades, and new therapeutic strategies aiming to enhance BDNF function have been shown to exert a rapid and effective antidepressant action.

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Metabotropic glutamate 2/3 receptor antagonists improve behavioral and prefrontal dopaminergic alterations in the chronic corticosterone-induced depression model in mice

Cited by 84 publications

References 64 publications

Defensive responses of Brandt's voles (Lasiopodomys brandtii) to chronic predatory stress

Defensive responses of Brandt's voles (Lasiopodomys brandtii) to chronic predatory stress

The Antidepressant Effects of an mGlu2/3 Receptor Antagonist and Ketamine Require AMPA Receptor Stimulation in the mPFC and Subsequent Activation of the 5-HT Neurons in the DRN

New hypothesis and treatment targets of depression: an integrated view of key findings

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