Yam Code

New Paste Browse

https://www.selleckchem.com/products/leupeptin-hemisulfate.html This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.BACKGROUND AND PURPOSE Hispidulin is a flavonoid isolated from Clerodendrum inerme that was found to remit intractable motor tics. Previously, we have found that hispidulin attenuates hyperlocomotion and the disrupted prepulse inhibition (PPI) induced by methamphetamine and N-methyl-d-aspartate (NMDA) receptor blockers, two phenotypes of schizophrenia resembling positive symdromes. Hispidulin can inhibit catechol-O-methyltransferase (COMT), a dopamine-metabolizing enzyme in the prefrontal cortex (PFC) that is important for social interaction. Here, we investigated whether hispidulin would affect social withdrawal, one dimension of negative symptoms in schizophrenia. EXPERIMENTAL APPROACH We examined whether acute administration of hispidulin would attenuate social withdrawal in two mouse models, juvenile isolated disrupted-in-schizophrenia-1 mutant (mutDISC1) mice and chronic phencyclidine (PCP)-treated naïve mice. KEY RESULTS In chronic PCP-treated mice, hispidulin (10 mg/kg, i.p.) attenuated social withdrawal in a manner prevented by a dopamine D1 receptor (D1 R) antagonist (SCH 23390, 0.02 mg/kg, i.p.) and mimicked by a selective COMT inhibitor, OR-486 (10 mg/kg, i.p.). Hispidulin increased extracellular dopamine levels in the PFC of chronic PCP-treated mice. In isolated mutDISC1 mice, hispidulin also rescued social withdrawal. In both models, intra-PFC microinjection of a D1 R agonist (SKF81297 10 nmol/mouse/bilateral) reversed the impairment of Ser897 phosphorylation at the NR1 subunit of NMDA receptors, suggesting the association between NR1 Ser897 -phosphorylation and D1 R activation in the PFC exits in both models. CONCLUSIONS AND IMPLICATIONS Hispidulin rescues social withdrawal by activating D1 Rs indirectly through elevated dopamine levels in the PFC by COMT inhibition. Thi

Paste Settings

Paste Title : [Optional]

Paste Folder : [Optional]

Syntax Highlighting : [Optional]

Paste Expiration : [Optional]

Paste Status : [Optional]

Password : [Optional]

Description: [Optional]

Tags: [Optional]

Encrypt Paste (?)

You are currently not logged in, this means you can not edit or delete anything you paste. Sign Up or Login

Paste Settings

Site Languages