Antidepressant-like effects of mGluR1 and mGluR5 antagonists in the rat forced swim and the mouse tail suspension tests

Belozertseva, Irina; Kos, Tomasz; Popik, Piotr; Danysz, Wojciech; Bespalov, Anton

doi:10.1016/j.euroneuro.2006.03.002

Cited by 171 publications

(102 citation statements)

References 40 publications

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“…s1R ligands exert potent neuromodulation on excitatory neurotransmitter systems, such as the glutamate and dopamine systems, which are both involved in behavioral despair (Belozertseva et al, 2007;Gershon et al, 2007). Selective s1R agonists cause antidepressant-like effects on rats in swim tests (Gudelsky, 1995;Urani et al, 2001), noting that DHEA and DHEAS are also potent s1R agonists (Urani et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

DHEA Lessens Depressive-Like Behavior via GABA-ergic Modulation of the Mesolimbic System

Genud

Merenlender

Gispan-Herman

et al. 2008

Neuropsychopharmacol

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Alterations in the levels of dehydroepiandrosterone (DHEA) in the brain can allosterically modulate g-aminobutyric-acid-type-A (GABA A R), N-methyl-D-aspartate (NMDAR), and Sigma-1 (s1R) receptors. In humans, DHEA has antidepressive effects; however, the mechanism is unknown. We examined whether alterations in DHEA also occur in an animal model of depression, the Flinders-sensitiveline (FSL) rats, with the intention of determining the brain site of DHEA action and its antidepressant mechanism. We discovered that DHEA levels were lower in some brain regions involved with depression of FSL rats compared to Sprague-Dawley (SD) controls. Moreover, DHEA (1 mg/kg IP for 14 days)-treated FSL rats were more mobile in the forced swim test than FSL controls. In the NAc and VTA, significant changes were observed in the levels of the d-subunit of GABA A , but not of s1R mRNA, in FSL rats compared to SD rats. The d-subunit controls the sensitivity of the GABA A R to the neurosteroid. Indeed, treatment (14 days) of FSL rats with the GABA A agonist muscimol (0.5 mg/kg), together with DHEA (a negative modulator of GABA A ), reversed the effect of DHEA on immobility in the swim test. Perfusion of DHEA sulfate (DHEAS) (3 nM and 30 nM for 14 days) into the VTA and NAc of FSL rats improved their performance in the swim test for at least 3 weeks post-treatment. Our results imply that alterations in DHEA are involved in the pathophysiology of depression and that the antidepressant action of DHEA is mediated via GABA A Rs in the NAc and VTA.

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Section: Introductionmentioning

confidence: 99%

DHEA Lessens Depressive-Like Behavior via GABA-ergic Modulation of the Mesolimbic System

Genud

Merenlender

Gispan-Herman

et al. 2008

Neuropsychopharmacol

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“…As shown in Table 2 the selective orthosteric antagonist for this receptor, MPEP (Gasparini et al, 1999) and its derivative MTEP (Cosford et al, 2003), were active in the forced swim test in both rats and mice, and in the tail suspension test in mice (Belozertseva et al, 2007;Li et al, 2006;Palucha et al, 2005;Pilc et al, 2002;Tatarczyńska et al, 2001). Moreover, in the olfactory bulbectomy model of depression it was shown that chronic administration of those substances evoked behavioural effects similar to those observed after the administration of ADDs administration (Palucha et al, 2005;Pilc et al, 2002;Wieronska et al, 2005 in the hippocampus of the rat brain, which remains in line with the neurotrophic theory of depression (Legutko et al, 2006 The antidepressant effects could be evoked not only after administration of mGlu 5 receptor antagonists, but also after blockade of mGlu 1 receptor subtype, the second representative of group I mGlu receptors, as its antagonist EMQMCM was effective in the tail suspension and forced swim test in mice (Belozertseva et al, 2007). The role of the first group of mGlu receptors in depression and in the mechanism of action of ADDs is confirmed by experiments illustrating the changes in both the reactivity and expression of the mGlu 1 and mGlu 5 receptors after chronic ADDs treatment in both rats and mice (Pilc et al, 1998;Smiałowska et al, 2002;Zahorodna et al, 1999).…”

Section: The Role Of Group I Mglu Receptors In the Mechanism Of Actiomentioning

confidence: 99%

Depression Viewed as a GABA/Glutamate Imbalance in the Central Nervous System

Wierońska¹,

Pałucha-Poniewiera²,

Nowak³

et al. 2012

Clinical, Research and Treatment Approaches to Affective Disorders

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“…Group I mGluRs are also implicated in the pathogenesis of depression [38] . A number of reports consistently showed that mGluR1 and especially mGluR5 antagonists produced antidepressant-like effects in various stress models [39][40][41][42][43] . Similarly, mGluR5 knockout mice displayed an antidepressant-like behavioral phenotype [42] .…”

Section: Tyrosine Phosphorylation Of Glutamate Receptors In Major Depmentioning

confidence: 99%

Tyrosine phosphorylation of glutamate receptors by non-receptor tyrosine kinases: roles in depression-like behavior

Mao

Wang

2016

Neurotransmitter

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Several key members of the non-receptor tyrosine kinase (nRTK) family are abundantly present within excitatory synapses in the mammalian brain. These neuron-enriched nRTKs interact with glutamate receptors and phosphorylate the receptors at tyrosine sites. The N-methyl-D-aspartate receptor is a direct substrate of nRTKs and has been extensively investigated in its phosphorylation responses to nRTKs. The -amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor is the other glutamate receptor subtype that is subject to nRTK-mediated tyrosine phosphorylation. Recently, group I metabotropic glutamate receptors (mGluR1/5) were found to be sensitive to nRTKs. Robust tyrosine phosphorylation may occur in C-terminal tails of mGluR5. Tyrosine phosphorylation of glutamate receptors is either constitutive or induced activity-dependently by changing cellular and/or synaptic input. Through inducing tyrosine phosphorylation, nRTKs regulate trafficking, subcellular distribution, and function of modified receptors. Available data show that nRTK-glutamate receptor interactions and tyrosine phosphorylation of the receptors undergo drastic adaptations in mood disorders such as major depressive disorder. The remodeling of the nRTK-glutamate receptor interplay contributes to the long-lasting pathophysiology and symptomology of depression. This review summarizes the recent progress in tyrosine phosphorylation of glutamate receptors and analyzes the role of nRTKs in regulating glutamate receptors and depression-like behavior.

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Antidepressant-like effects of mGluR1 and mGluR5 antagonists in the rat forced swim and the mouse tail suspension tests

Cited by 171 publications

References 40 publications

DHEA Lessens Depressive-Like Behavior via GABA-ergic Modulation of the Mesolimbic System

DHEA Lessens Depressive-Like Behavior via GABA-ergic Modulation of the Mesolimbic System

Depression Viewed as a GABA/Glutamate Imbalance in the Central Nervous System

Tyrosine phosphorylation of glutamate receptors by non-receptor tyrosine kinases: roles in depression-like behavior

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