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Inhibition of glutamine synthetase in the central nucleus of the amygdala induces anhedonic behavior and recurrent seizures in a rat model of mesial temporal lobe epilepsy
被引:13
作者:
Gruenbaum, Shaun E.
[1
]
Wang, Helen
[1
]
Zaveri, Hitten P.
[2
]
Tang, Amber B.
[1
]
Lee, Tih-Shih W.
[3
]
Eid, Tore
[1
]
Dhaher, Roni
[1
]
机构:
[1] Yale Univ, Sch Med, Dept Lab Med, New Haven, CT 06520 USA
[2] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06520 USA
[3] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06520 USA
基金:
美国国家卫生研究院;
关键词:
Anhedonia;
Epilepsy;
Glutamine synthetase;
Central amygdala;
Sucrose preference;
STATUS EPILEPTICUS;
ANTIEPILEPTIC DRUGS;
DEPRESSIVE BEHAVIOR;
SUICIDAL IDEATION;
GLUCOCORTICOID-RECEPTOR;
ETHANOL-CONSUMPTION;
PILOCARPINE MODEL;
BRAIN;
EXPRESSION;
ACID;
D O I:
10.1016/j.yebeh.2015.07.015
中图分类号:
B84 [心理学];
C [社会科学总论];
Q98 [人类学];
学科分类号:
03 ;
0303 ;
030303 ;
04 ;
0402 ;
摘要:
The prevalence of depression and suicide is increased in patients with mesial temporal lobe epilepsy (MTLE); however, the underlying mechanism remains unknown. Anhedonia, a core symptom of depression that is predictive of suicide, is common in patients with MTLE. Glutamine synthetase, an astrocytic enzyme that metabolizes glutamate and ammonia to glutamine, is reduced in the amygdala in patients with epilepsy and depression and in suicide victims. Here, we sought to develop a novel model of anhedonia in MTLE by testing the hypothesis that deficiency in glutamine synthetase in the central nucleus of the amygdala (CeA) leads to epilepsy and comorbid anhedonia. Nineteen male Sprague-Dawley rats were implanted with an osmotic pump infusing either the glutamine synthetase inhibitor methionine sulfoximine [MSO (n = 12)] or phosphate buffered saline [PBS (n = 7)] into the right CeA. Seizure activity was monitored by video-intracranial electroencephalogram (EEG) recordings for 21 days after the onset of MSO infusion. Sucrose preference, a measure of anhedonia, was assessed after 21 days. Methionine sulfoximine-infused rats exhibited recurrent seizures during the monitoring period and showed decreased sucrose preference over days when compared with PBS-infused rats (p < 0.01). Water consumption did not differ between the PBS-treated group and the MSO-treated group. Neurons were lost in the CeA, but not the medial amygdala, lateral amygdala, basolateral amygdala, or the hilus of the dentate gyrus, in the MSO-treated rats. The results suggest that decreased glutamine synthetase activity in the CeA is a possible common cause of anhedonia and seizures in TLE. We propose that the MSO CeA model can be used for mechanistic studies that will lead to the development and testing of novel drugs to prevent seizures, depression, and suicide in patients with TLE. (C) 2015 Elsevier Inc. All rights reserved.
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页码:96 / 103
页数:8
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