首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Chronic inositol increases striatal D(2) receptors but does not modify dexamphetamine-induced motor behavior. Relevance to obsessive-compulsive disorder.
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Chronic inositol increases striatal D(2) receptors but does not modify dexamphetamine-induced motor behavior. Relevance to obsessive-compulsive disorder.

机译:慢性肌醇增加纹状体D(2)受体,但不会修改右旋苯丙胺诱导的运动行为。与强迫症有关。

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A large body of evidence suggests that the neuropathology of obsessive-compulsive disorder (OCD) lies in the complex neurotransmitter network of the cortico-striatal-thalamo-cortical (CSTC) circuit, where dopamine (DA), serotonin (5HT), glutamate (Glu), and gamma-amino butyric acid (GABA) dysfunction have been implicated in the disorder. Chronic inositol has been found to be effective in specific disorders that respond to selective serotonin reuptake inhibitors (SSRIs), including OCD, panic, and depression. This selective mechanism of action is obscure. Since nigro-striatal DA tracts are subject to 5HT(2) heteroreceptor regulation, one possible mechanism of inositol in OCD may involve its effects on inositol-dependent receptors, especially the 5HT(2) receptor, and a resulting effect on DA pathways in the striatum. In order to investigate this possible interaction, we exposed guinea pigs to oral inositol (1.2 g/kg) for 12 weeks. Subsequently, effects on locomotor behavior (LB) and stereotype behavior (SB), together with possible changes to striatal 5HT(2) and D(2) receptor function, were determined. In addition, the effects of chronic inositol on dexamphetamine (DEX)-induced motor behavior were evaluated. Acute DEX (3 mg/kg, ip) induced a significant increase in both SB and LB, while chronic inositol alone did not modify LA or SB. The behavioral response to DEX was also not modified by chronic inositol pretreatment. However, chronic inositol induced a significant increase in striatal D(2) receptor density (B(max)) with a slight, albeit insignificant, increase in 5HT(2) receptor density. This suggests that D(2) receptor upregulation may play an important role in the behavioral effects of inositol although the role of the 5HT(2) receptor in this response is questionable.
机译:大量证据表明,强迫症(OCD)的神经病理学位于皮质-纹状体-丘脑-皮质(CSTC)回路的复杂神经递质网络中,其中多巴胺(DA),血清素(5HT),谷氨酸( Glu)和γ-氨基丁酸(GABA)功能障碍已与该疾病有关。慢性肌醇已发现在对选择性5-羟色胺再摄取抑制剂(SSRI)有反应的特定疾病中有效,包括强迫症,恐慌和抑郁症。这种选择性的作用机制是模糊的。由于黑纹状体DA束受5HT(2)异源受体调节,因此强迫症中肌醇的一种可能机制可能涉及其对肌醇依赖性受体(尤其是5HT(2)受体)的影响,以及对肌醇中DA途径的影响。纹状体。为了研究这种可能的相互作用,我们将豚鼠暴露于口服肌醇(1.2 g / kg)12周。随后,确定对运动行为(LB)和定型行为(SB)的影响,以及对纹状体5HT(2)和D(2)受体功能的可能改变。此外,评估了慢性肌醇对右旋苯丙胺(DEX)诱导的运动行为的影响。急性DEX(3 mg / kg,ip)会导致SB和LB显着增加,而单独的慢性肌醇不会改变LA或SB。慢性肌醇预处理也不能改变对DEX的行为反应。但是,慢性肌醇诱导纹状体D(2)受体密度(B(max))显着增加,尽管5HT(2)受体密度略有增加,尽管微不足道。这表明D(2)受体上调可能在肌醇的行为效应中起重要作用,尽管5HT(2)受体在该反应中的作用值得怀疑。

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