NMDA receptor antagonists attenuate the proconvulsant effect of juvenile social isolation in male mice

Amiri, Shayan. and Haj-Mirzaian, Arya. and Amini-Khoei, Hossein. and Momeny, Majid. and Shirzadian, Armin. and Rahimi Balaei, Maryam. and Zarrinrad, Ghazaleh. and Ghazi-Khansari, Mahmoud. and Azizi, Romina. and Dehpour, Ahmad Reza. and Ejtemaei Mehr, Shahram. (2016) NMDA receptor antagonists attenuate the proconvulsant effect of juvenile social isolation in male mice. Brain research bulletin, 121.

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Abstract

Experiencing psychosocial stress inearly life, suchas social isolationstress (SIS), is knowntohavenegative enduring effects on the development of the brain and behavior. In addition to anxiety and depressive-like behaviors, we previously showed that juvenile SIS increases susceptibility to pentylenetetrazole (PTZ)- induced seizures in mice through enhancing the nitrergic system activity in the hippocampus. In this study, we investigated the possible involvement of N-methyl-d-aspartate (NMDA) receptors in proconvulsant effects of juvenile SIS. Applying 4 weeks of SIS to juvenile male mice at postnatal day 21–23, we observed an increased susceptibility to PTZ as well as anxiety and depressive-like behaviors in adult mice. Intraperitoneal (i.p.) administration of NMDA receptor antagonists, MK-801 (0.05 mg/kg) and ketamine (0.5 mg/kg), reversed the proconvulsant effects of SIS in Isolated (and not social) housed animals. Coadministration of non-effective doses of nitric oxide synthase (NOS) inhibitors, 7NI (25 mg/kg) and L-NAME (10 mg/kg), with NMDA receptor antagonists, MK-801 (0.01 mg/kg) and ketamine (0.1 mg/kg) attenuated the proconvulsant effects of juvenile SIS only in isolated housed mice. Also, using real time RT-PCR, we showed that hippocampal upregulation of NR2B subunit of NMDA receptor may play a critical role in proconvulsant effects of juvenile SIS by dysregulation of NMDA/NO pathway. In conclusion, results of present study revealed that experiencing SIS during adolescence predisposes the co-occurrence of seizure disorders with psychiatric comorbidities and also, alteration of NMDA receptor structure and function in hippocampus plays a role in proconvulsant effects of juvenile SIS through enhancing the NMDA/NO pathway

Item Type: Article
Uncontrolled Keywords: Juvenile social isolation stress NMDA receptor,Nitric oxide,PTZ-induced seizures,NR2B subunit
Subjects: WM Psychiatry
QV pharmacology
Divisions: Reserach Vice-Chancellar Department > Cellular and Molecular Research Center
Depositing User: Users 1 not found.
Date Deposited: 31 Dec 2017 06:15
Last Modified: 30 Jan 2018 05:37
URI: http://eprints.skums.ac.ir/id/eprint/6760

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