Pharmacological evidence for the involvement of the NMDA receptor and nitric oxide pathway in the antidepressant-like effect of lamotrigine in the mouse forced swimming test

Ostadhadi, Sattar; Ahangari, Mohammad; Nikoui, Vahid; Javidan, Abbas Norouzi; Zolfaghari, Samira; Jazaeri, Farahnaz; Chamanara, Mohsen; Akbarian, Reyhaneh; Dehpour, Ahmad Reza

doi:10.1016/j.biopha.2016.05.035

Cited by 39 publications

(11 citation statements)

References 75 publications

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“…These findings suggest that the antidepressant-like effect of this extract involves nitric oxide signaling. A similar mechanism has been reported for lamotrigine, which also has antidepressant-like activity [ 99 ].…”

Section: Antidepressant-like Effects Of Flavonoids In Plant Extracsupporting

confidence: 69%

Advances in the Preclinical Study of Some Flavonoids as Potential Antidepressant Agents

Germán-Ponciano

Rosas-Sánchez

Rivadeneyra-Domínguez

et al. 2018

Scientifica

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Flavonoids are phenolic compounds found commonly in plants that protect them against the negative effects of environmental insults. These secondary metabolites have been widely studied in preclinical research because of their biological effects, particularly as antioxidant agents. Diverse flavonoids have been studied to explore their potential therapeutic effects in the treatment of disorders of the central nervous system, including anxiety and depression. The present review discusses advances in the study of some flavonoids as potential antidepressant agents. We describe their behavioral, physiological, and neurochemical effects and the apparent mechanism of action of their preclinical antidepressant-like effects. Natural flavonoids produce antidepressant-like effects in validated behavioral models of depression. The mechanism of action of these effects includes the activation of serotonergic, dopaminergic, noradrenergic, and γ-aminobutyric acid-ergic neurotransmitter systems and an increase in the production of neural factors, including brain-derived neurotrophic factor and nerve growth factor. Additionally, alterations in the function of tropomyosin receptor kinase B and activity of the enzyme monoamine oxidase A have been reported. In conclusion, preclinical research supports the potential antidepressant effects of some natural flavonoids, which opens new possibilities of evaluating these substances to develop complementary therapeutic alternatives that could ameliorate symptoms of depressive disorders in humans.

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Section: Antidepressant-like Effects Of Flavonoids In Plant Extracsupporting

confidence: 69%

Advances in the Preclinical Study of Some Flavonoids as Potential Antidepressant Agents

Germán-Ponciano

Rosas-Sánchez

Rivadeneyra-Domínguez

et al. 2018

Scientifica

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“…Venlafaxine also enhanced antidepressant-like effect combined with MB [35]. The sGC regulated the cGMP concentration, while cGMP was also dependent on PDE5, which was involved in catalyzing cGMP to GMP [55,56]. Sildenafil (a PDE5 inhibitor) could increase the level of cGMP [55], and it reversed antidepressant-like effect of YJ in the present study.…”

Section: Discussionmentioning

confidence: 65%

NMDA receptors and L-arginine/nitric oxide/cyclic guanosine monophosphate pathway contribute to the antidepressant-like effect of Yueju pill in mice

et al. 2019

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The present study aims to evaluate the involvement of N-methyl-d-aspartate receptor and nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) system in antidepressant-like effects of Yueju pill (YJ), a Chinese herbal medicine. The immobility time in tail suspension test (TST) and forced swim test (FST) was used to assess the antidepressant effects. Prior administration of L-arginine (750 mg/kg, intraperitoneal [i.p.]), a NO synthase substrate that enhances NO signaling or sildenafil (5 mg/kg, i.p.), a phosphodiesterase 5 inhibitor that enhances cGMP, blunted the antidepressant-like activity of YJ (2.7 g/kg, i.g.). Co-treatment of ineffective dose of YJ (1.35 g/kg, i.g.) with one of the reagents that suppress the NO/cGMP signaling, including methylene blue (10 mg/kg, i.p.), an inhibitor of NO synthase; 7-NI (7-nitroinidazole, 30 mg/kg, i.p.), an nNOS specific inhibitor; L-NAME (10 mg/kg, i.p.), a non-specific inhibitor of NO synthase; and MK-801 (0.05 mg/kg, i.p.), an NMDA receptor antagonist, reduced the immobility time in TST and FST, compared with those in vehicle or single drug treatment groups. Neither above drugs alone or co-administrated with YJ affected locomotor activity or anxiety behavior in open field test. Thus, our results suggest that the antidepressant-like action of YJ may depend on the inhibition of NMDA/NO/cGMP pathway.

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“…21 Lamotrigine acts by inhibiting glutamate by blocking N-methyl-D-aspartate (NMDA) receptors and inhibiting sodium-gated channels. 28,29 Kemp et al 8 hypothesized that lamotrigine may disrupt the glutamate balance within the cortico-striato-thalamic-cortical network resulting in the development of OCD. It is also unclear as to why lamotrigine induces OCD in some patients while it ameliorates these symptoms in others.…”

Section: Discussionmentioning

confidence: 99%

Lamotrigine-induced obsessive-compulsive disorder in patients with bipolar disorder

Sharma

Doobay

2018

CNS Spectr.

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IntroductionLamotrigine is a commonly used drug in the treatment of bipolar disorder. Although there are reports of its effectiveness in the management of bipolar disorder and comorbid obsessive-compulsive disorder (OCD), lamotrigine has also been associated with obsessionality in patients with bipolar disorder.MethodsCharts of 8 patients with bipolar disorder who had de novo onset of obsessions and compulsions after the use of lamotrigine were reviewed. The Naranjo scale was used to assess the likelihood of patients developing OCD due to lamotrigine use.ResultsTwo to 8 months after the initiation of lamotrigine, patients with no such prior history developed obsessions and compulsions meeting the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnostic criteria for medication-induced OCD. In all except 1 patient, the symptoms resolved within a month of lamotrigine discontinuation.ConclusionsSome patients with bipolar disorder may develop OCD after initiation of lamotrigine. Due to the inherent limitations of a case series, the findings should be interpreted with caution.

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Pharmacological evidence for the involvement of the NMDA receptor and nitric oxide pathway in the antidepressant-like effect of lamotrigine in the mouse forced swimming test

Cited by 39 publications

References 75 publications

Advances in the Preclinical Study of Some Flavonoids as Potential Antidepressant Agents

Advances in the Preclinical Study of Some Flavonoids as Potential Antidepressant Agents

NMDA receptors and L-arginine/nitric oxide/cyclic guanosine monophosphate pathway contribute to the antidepressant-like effect of Yueju pill in mice

Lamotrigine-induced obsessive-compulsive disorder in patients with bipolar disorder

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