Positive symptom phenotypes appear progressively in “EDiPS”, a new animal model of the schizophrenia prodrome

Abstract An increase in dopamine (DA) synthesis capacity in the dorsal striatum (DS) during the prodromal stage of schizophrenia becomes more pronounced as patients progress to the full disorder. Understanding this progression is critical to intervening in disease course. We developed an animal mode...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Alice Petty, Xiaoying Cui, Asad Ali, Zilong Du, Sunil Srivastav, James P. Kesby, Deniz Kirik, Oliver Howes, Darryl Eyles
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/041501d82fe64bce8596a7893fcb044b
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:041501d82fe64bce8596a7893fcb044b
record_format	dspace
spelling	oai:doaj.org-article:041501d82fe64bce8596a7893fcb044b2021-12-02T11:02:37ZPositive symptom phenotypes appear progressively in “EDiPS”, a new animal model of the schizophrenia prodrome10.1038/s41598-021-83681-42045-2322https://doaj.org/article/041501d82fe64bce8596a7893fcb044b2021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83681-4https://doaj.org/toc/2045-2322Abstract An increase in dopamine (DA) synthesis capacity in the dorsal striatum (DS) during the prodromal stage of schizophrenia becomes more pronounced as patients progress to the full disorder. Understanding this progression is critical to intervening in disease course. We developed an animal model—Enhanced Dopamine in Prodromal Schizophrenia (EDiPS)—which uses a genetic construct to increase DA synthesis capacity in the DS of male rats. We assessed pre-pulse inhibition (PPI) and amphetamine (AMPH)-induced locomotion (0.6 mg/kg) in EDiPS animals longitudinally after post-natal day 35 (when the EDiPS construct is administered). We also assessed their response to repeated acute restraint stress. In adult EDiPS animals, we measured baseline and evoked extracellular DA levels, and their stereotyped responses to 5 mg/kg AMPH. AMPH-induced hyperlocomotion was apparent in EDiPS animals 6-weeks after construct administration. There was an overall PPI deficit in EDiPS animals across all timepoints, however the stress response of EDiPS animals was unaltered. Adult EDiPS animals show normal baseline and potassium-evoked DA release in the DS. These findings suggest that key behavioural phenotypes in EDiPS animals show a progressive onset, similar to that demonstrated by patients as they transition to schizophrenia. The EDiPS model could therefore be used to investigate the molecular mechanisms underlying the prodrome of schizophrenia.Alice PettyXiaoying CuiAsad AliZilong DuSunil SrivastavJames P. KesbyDeniz KirikOliver HowesDarryl EylesNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Alice Petty Xiaoying Cui Asad Ali Zilong Du Sunil Srivastav James P. Kesby Deniz Kirik Oliver Howes Darryl Eyles Positive symptom phenotypes appear progressively in “EDiPS”, a new animal model of the schizophrenia prodrome
description	Abstract An increase in dopamine (DA) synthesis capacity in the dorsal striatum (DS) during the prodromal stage of schizophrenia becomes more pronounced as patients progress to the full disorder. Understanding this progression is critical to intervening in disease course. We developed an animal model—Enhanced Dopamine in Prodromal Schizophrenia (EDiPS)—which uses a genetic construct to increase DA synthesis capacity in the DS of male rats. We assessed pre-pulse inhibition (PPI) and amphetamine (AMPH)-induced locomotion (0.6 mg/kg) in EDiPS animals longitudinally after post-natal day 35 (when the EDiPS construct is administered). We also assessed their response to repeated acute restraint stress. In adult EDiPS animals, we measured baseline and evoked extracellular DA levels, and their stereotyped responses to 5 mg/kg AMPH. AMPH-induced hyperlocomotion was apparent in EDiPS animals 6-weeks after construct administration. There was an overall PPI deficit in EDiPS animals across all timepoints, however the stress response of EDiPS animals was unaltered. Adult EDiPS animals show normal baseline and potassium-evoked DA release in the DS. These findings suggest that key behavioural phenotypes in EDiPS animals show a progressive onset, similar to that demonstrated by patients as they transition to schizophrenia. The EDiPS model could therefore be used to investigate the molecular mechanisms underlying the prodrome of schizophrenia.
format	article
author	Alice Petty Xiaoying Cui Asad Ali Zilong Du Sunil Srivastav James P. Kesby Deniz Kirik Oliver Howes Darryl Eyles
author_facet	Alice Petty Xiaoying Cui Asad Ali Zilong Du Sunil Srivastav James P. Kesby Deniz Kirik Oliver Howes Darryl Eyles
author_sort	Alice Petty
title	Positive symptom phenotypes appear progressively in “EDiPS”, a new animal model of the schizophrenia prodrome
title_short	Positive symptom phenotypes appear progressively in “EDiPS”, a new animal model of the schizophrenia prodrome
title_full	Positive symptom phenotypes appear progressively in “EDiPS”, a new animal model of the schizophrenia prodrome
title_fullStr	Positive symptom phenotypes appear progressively in “EDiPS”, a new animal model of the schizophrenia prodrome
title_full_unstemmed	Positive symptom phenotypes appear progressively in “EDiPS”, a new animal model of the schizophrenia prodrome
title_sort	positive symptom phenotypes appear progressively in “edips”, a new animal model of the schizophrenia prodrome
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/041501d82fe64bce8596a7893fcb044b
work_keys_str_mv	AT alicepetty positivesymptomphenotypesappearprogressivelyinedipsanewanimalmodeloftheschizophreniaprodrome AT xiaoyingcui positivesymptomphenotypesappearprogressivelyinedipsanewanimalmodeloftheschizophreniaprodrome AT asadali positivesymptomphenotypesappearprogressivelyinedipsanewanimalmodeloftheschizophreniaprodrome AT zilongdu positivesymptomphenotypesappearprogressivelyinedipsanewanimalmodeloftheschizophreniaprodrome AT sunilsrivastav positivesymptomphenotypesappearprogressivelyinedipsanewanimalmodeloftheschizophreniaprodrome AT jamespkesby positivesymptomphenotypesappearprogressivelyinedipsanewanimalmodeloftheschizophreniaprodrome AT denizkirik positivesymptomphenotypesappearprogressivelyinedipsanewanimalmodeloftheschizophreniaprodrome AT oliverhowes positivesymptomphenotypesappearprogressivelyinedipsanewanimalmodeloftheschizophreniaprodrome AT darryleyles positivesymptomphenotypesappearprogressivelyinedipsanewanimalmodeloftheschizophreniaprodrome
_version_	1718396272991272960

Positive symptom phenotypes appear progressively in “EDiPS”, a new animal model of the schizophrenia prodrome

Ejemplares similares