Calbindin Deficits May Underlie Dissociable Effects of 5-HT₆ and mGlu₇ Antagonists on Glutamate and Cognition in a Dual-Hit Neurodevelopmental Model for Schizophrenia.

ABSTRACT: Despite several compounds entering clinical trials for the negative and cognitive symptoms of schizophrenia, few have progressed beyond phase III. This is partly attributed to a need for improved preclinical models, to understand disease and enable predictive evaluation of novel therapeutics. To this end, one recent approach incorporates "dual-hit" neurodevelopmental insults like neonatal phencyclidine plus isolation rearing (PCP-Iso). Glutamatergic dysfunction contributes to schizophrenia pathophysiology and may represent a treatment target, so we used enzyme-based microsensors to evaluate basal- and drug-evoked glutamate release in hippocampal slices from rats that received neonatal PCP and/or isolation rearing. 5-HT₆ antagonist-evoked glutamate release (thought to be mediated

SUBMITTER: Shortall SE 

PROVIDER: S-EPMC7340678 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature