Modulation of mGlu5 improves sensorimotor gating deficits in rats neonatally treated with quinpirole through changes in dopamine D2 signaling.
Modulation of mGlu5 improves sensorimotor gating deficits in rats neonatally treated with quinpirole through changes in dopamine D2 signaling.
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DOI：
10.1016/j.pbb.2021.173292
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发表时间：
2021-12
影响因子：
3.6
通讯作者：
Gass, Justin T.
中科院分区：
文献类型：
--
作者：
Brown, Russell W.;Varnum, Christopher G.;Wills, Liza J.;Peeters, Loren D.;Gass, Justin T.
关键词：
本研究分析了代谢型谷氨酸受体5型（mGlu 5）3-氰基-N-（1，3-二苯基-1H-吡唑-5-基）苯甲酰胺（CDPPB）的正变构调节剂是否会减轻精神分裂症（SZ）新生儿喹吡罗（NQ）模型中背侧纹状体和前额叶皮层（PFC）中前脉冲抑制（PPI）的缺陷并影响多巴胺（DA）D2信号。雄性和雌性Sprague-Dawley大鼠用生理盐水（NS）或盐酸喹吡罗（1 mg/kg; NQ）给药。出生后第1-21天（P）的DAD 2受体激动剂。将大鼠饲养至P44，并从P44-P48对PPI进行行为测试。在每次试验之前，向大鼠皮下（sc）施用盐水或CDPPB（10 mg/kg或30 mg/kg）。在P50，给予大鼠CDPPB或生理盐水后进行自发活动试验。在P51，背侧纹状体和PFC的arrestin-2（βA-2）和磷酸化AKT蛋白水平进行了评估。NQ处理的大鼠表现出PPI的显著不足，其通过30 mg/kg剂量的CDPPB缓解至对照水平。CDPPB对自发活动无明显影响。NQ处理增加了背侧纹状体和PFC中的βA-2并降低了磷酸化AKT。30 mg/kg剂量的CDPPB显著逆转了背侧纹状体中的βA-2和PFC中的PFC和磷酸化AKT的变化，与对照组相当。与对照组相比，两种剂量的CDPPB均使PFC中的磷酸化AKT减少。该研究揭示了mGlu 5阳性变构调节剂在SZ的NQ模型中有效减轻PPI缺陷和纹状体DAD 2信号传导。
This study analyzed whether the positive allosteric modulator of metabotropic glutamate receptor type 5 (mGlu5) 3-Cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (CDPPB) would alleviate deficits in prepulse inhibition (PPI) and affect dopamine (DA) D2 signaling in the dorsal striatum and prefrontal cortex (PFC) in the neonatal quinpirole (NQ) model of schizophrenia (SZ). Male and female Sprague-Dawley rats were neonatally treated with either saline (NS) or quinpirole HCL (1 mg/kg; NQ). a DAD2 receptor agonist from postnatal days (P) 1–21. Rats were raised to P44 and behaviorally tested on PPI from P44-P48. Before each trial, rats were subcutaneous (sc) administered saline or CDPPB (10 mg/kg or 30 mg/kg). On P50, rats were given a spontaneous locomotor activity test after CDPPB or saline administration. On P51, the dorsal striatum and PFC were evaluated for both arrestin-2 (βA-2) and phospho-AKT protein levels. NQ-treated rats demonstrated a significant deficit in PPI, which was alleviated to control levels by the 30 mg/kg dose of CDPPB. There were no significant effects of CDPPB on locomotor activity. NQ treatment increased βA-2 and decreased phospho-AKT in both the dorsal striatum and PFC. The 30 mg/kg dose of CDPPB significantly reversed changes in βA-2 in the dorsal striatum and PFC and phospho-AKT in the PFC equivalent to controls. Both doses of CDPPB produced a decrease of phospho-AKT in the PFC compared to controls. This study revealed that a mGlu5 positive allosteric modulator was effective to alleviate PPI deficits and striatal DAD2 signaling in the NQ model of SZ.
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DOI：
10.3390/molecules16032097
发表时间：
2011-03-02
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Cleva RM;Olive MF
通讯作者：
Olive MF
影响因子：
4.7
作者：
Beggiato, Sarah;Tomasini, Maria Cristina;Ferraro, Luca
通讯作者：
Ferraro, Luca
影响因子：
6.1
作者：
Doria, J. G.;de Souza, J. M.;Ribeiro, F. M.
通讯作者：
Ribeiro, F. M.
影响因子：
7.6
作者：
During, Signe;Glenthoj, Birte Y.;Oranje, Bob
通讯作者：
Oranje, Bob
影响因子：
4.2
作者：
Conde-Ceide, Susana;Martinez-Viturro, Carlos M.;Lindsley, Craig W.
通讯作者：
Lindsley, Craig W.