Reduction in phencyclidine induced sensorimotor gating deficits in the rat following increased system xc⁻ activity in the medial prefrontal cortex.
Reduction in phencyclidine induced sensorimotor gating deficits in the rat following increased system xc⁻ activity in the medial prefrontal cortex.
复制标题
DOI：
10.1007/s00213-012-2926-3
复制
发表时间：
2013-04
影响因子：
3.4
通讯作者：
Baker, David A.
中科院分区：
文献类型：
--
作者：
Lutgen, Victoria;Qualmann, Krista;Resch, Jon;Kong, Linghai;Choi, SuJean;Baker, David A.
关键词：
Aspects of schizophrenia, including deficits in sensorimotor gating, have been linked to glutamate dysfunction and/or oxidative stress in the prefrontal cortex. System xc−, a cystine- glutamate antiporter, is a poorly understood mechanism that contributes to both cellular antioxidant capacity and glutamate homeostasis. Our goal was to determine whether increased system xc− activity within the prefrontal cortex would normalize a rodent measure of sensorimotor gating. In situ hybridization was used to map mRNA expression of xCT, the active subunit of system xc−, in the prefrontal cortex. Prepulse inhibition was used to measure sensorimotor gating; deficits in prepulse inhibition were produced using phencyclidine (0.3–3 mg/kg, sc). N-acetylcysteine (10–100 μM) and the system xc− inhibitor (S)-4-carboxyphenylglycine (CPG, 0.5 μM) were used to increase and decrease system xc− activity, respectively. The uptake of 14C-cystine into tissue punches obtained from the prefrontal cortex was used to assay system xc− activity. The expression of xCT mRNA in the prefrontal cortex was most prominent in a lateral band spanning primarily the prelimbic cortex. Although phencyclidine did not alter the uptake of 14C-cystine in prefrontal cortical tissue punches, intra-prefrontal cortical infusion of N-acetylcysteine (10–100 μM) significantly reduced phencyclidine- (1.5 mg/kg, sc) induced deficits in prepulse inhibition. N-acetylcysteine was without effect when co-infused with CPG (0.5 μM), indicating an involvement of system xc−. These results indicate that phencyclidine disrupts sensorimotor gating through system xc− independent mechanisms, but that increasing cystine-glutamate exchange in the prefrontal cortex is sufficient to reduce behavioral deficits produced by phencyclidine.
登录
查看更多内容
影响因子：
3.4
作者：
Chen, Hwei-Hsien;Stoker, Astrid;Markou, Athina
通讯作者：
Markou, Athina
影响因子：
11
作者：
FRANZEN, G;INGVAR, DH
通讯作者：
INGVAR, DH
影响因子：
2.5
作者：
Battaglia, G;Monn, JA;Schoepp, DD
通讯作者：
Schoepp, DD
影响因子：
64.8
作者：
Bezzi, P;Carmignoto, G;Volterra, A
通讯作者：
Volterra, A
影响因子：
10.6
作者：
Berk, Michael;Copolov, David;Bush, Ashley I.
通讯作者：
Bush, Ashley I.