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Effects of the antipsychotic paliperidone on stress-induced changes in the endocannabinoid system in rat prefrontal cortex

机译:抗精神病药酮酮对大鼠前额叶皮层内吲纳蛋白系统应激诱导变化的影响

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Objectives There is a need to explore novel mechanisms of action of existing/new antipsychotics. One potential candidate is the endocannabinoid system (ECS). The present study tried to elucidate the effects of the antipsychotic paliperidone on stress-induced ECS alterations. Methods Wister rats were submitted to acute/chronic restraint stress. Paliperidone (1mg/kg) was given prior each stress session. Cannabinoid receptors and endocannabinoids (eCBs) synthesis and degradation enzymes were measured in prefrontal cortex (PFC) samples by RT-PCR and Western Blot. Results In the PFC of rats exposed to acute stress, paliperidone increased CB1 receptor (CB1R) expression. Furthermore, paliperidone increased the expression of the eCB synthesis enzymes N-acylphosphatidylethanolamine- hydrolysing phospholipase D and DAGL, and blocked the stress-induced increased expression of the degrading enzyme fatty acid amide hydrolase. In chronic conditions, paliperidone prevented the chronic stress-induced down-regulation of CB1R, normalised DAGL expression and reverted stress-induced down-regulation of the 2-AG degrading enzyme monoacylglycerol lipase. ECS was analysed also in periphery. Acute stress decreased DAGL expression, an effect prevented by paliperidone. Contrarily, chronic stress increased DAGL and this effect was potentiated by paliperidone. Conclusions The results obtained described a preventive effect of paliperidone on stress-induced alterations in ECS. Considering the diverse alterations on ECS described in psychotic disease, targeting ECS emerges as a new therapeutic possibility.
机译:目的需要探索现有/新抗精神病药的新的行动机制。一个潜在的候选者是Endocannabinoid系统(ECS)。本研究试图阐明抗精神病药酮对应激诱导的ECS改变的影响。方法对大鼠提交急性/慢性约束压力。 Paliperidone(1mg / kg)在每个应力会议之前给出。通过RT-PCR和Western印迹在预偏转性皮层(PFC)样品中测量大麻素受体和内胆碱(ECBS)合成和降解酶。结果在暴露于急性应激的大鼠PFC中,paliperidone增加CB1受体(CB1R)表达。此外,Paliperidone增加了ECB合成酶N-酰基磷脂酰乙醇胺 - 水解磷脂酶D和DAGL的表达,并阻断了应力诱导的降解酶脂肪酸酰胺水解酶的表达。在慢性条件下,Paviperidone阻止了慢性应激诱导的CB1R的下调,归一化的DAG1表达和恢复应激诱导的2-Ag降解酶单酰基甘油脂肪酶的下调。 ECS也在外围分析。急性胁迫降低了DAGL表达,帕帕里酮预防的效果。相反,慢性应激增加了DAGL,并且PAPRIPERIDONE具有这种效果。结论所获得的结果描述了Paliperidone对ECS胁迫诱导的改变的预防作用。考虑到精神病疾病中描述的ECS的不同改变,靶向ECS作为一种新的治疗可能性。

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