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Enhanced Dopamine in Prodromal Schizophrenia (EDiPS): a new animal model of relevance to schizophrenia

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Enhanced Dopamine in Prodromal Schizophrenia (EDiPS) : a new animal model of relevance to schizophrenia. / Petty, Alice; Cui, Xiaoying; Tesiram, Yasvir; Kirik, Deniz; Howes, Oliver; Eyles, Darryl.

In: NPJ SCHIZOPHRENIA, Vol. 5, No. 1, 6, 01.12.2019.

Research output: Contribution to journalArticle

Harvard

Petty, A, Cui, X, Tesiram, Y, Kirik, D, Howes, O & Eyles, D 2019, 'Enhanced Dopamine in Prodromal Schizophrenia (EDiPS): a new animal model of relevance to schizophrenia', NPJ SCHIZOPHRENIA, vol. 5, no. 1, 6. https://doi.org/10.1038/s41537-019-0074-z

APA

Petty, A., Cui, X., Tesiram, Y., Kirik, D., Howes, O., & Eyles, D. (2019). Enhanced Dopamine in Prodromal Schizophrenia (EDiPS): a new animal model of relevance to schizophrenia. NPJ SCHIZOPHRENIA, 5(1), [6]. https://doi.org/10.1038/s41537-019-0074-z

Vancouver

Petty A, Cui X, Tesiram Y, Kirik D, Howes O, Eyles D. Enhanced Dopamine in Prodromal Schizophrenia (EDiPS): a new animal model of relevance to schizophrenia. NPJ SCHIZOPHRENIA. 2019 Dec 1;5(1). 6. https://doi.org/10.1038/s41537-019-0074-z

Author

Petty, Alice ; Cui, Xiaoying ; Tesiram, Yasvir ; Kirik, Deniz ; Howes, Oliver ; Eyles, Darryl. / Enhanced Dopamine in Prodromal Schizophrenia (EDiPS) : a new animal model of relevance to schizophrenia. In: NPJ SCHIZOPHRENIA. 2019 ; Vol. 5, No. 1.

Bibtex Download

@article{bfa71fadf6fe45f691e006157ba37f2b,
title = "Enhanced Dopamine in Prodromal Schizophrenia (EDiPS): a new animal model of relevance to schizophrenia",
abstract = "One of the most robust neurochemical abnormalities reported in patients living with schizophrenia is an increase in dopamine (DA) synthesis and release in the dorsal striatum (DS). Importantly, it appears that this increase progresses as a patient transitions from a prodromal stage to the clinical diagnosis of schizophrenia. Here we have recreated this pathophysiology in an animal model by increasing the capacity for DA synthesis preferentially within the DS. To achieve this we administer a genetic construct containing the rate-limiting enzymes in DA synthesis—tyrosine hydroxylase (TH), and GTP cyclohydrolase 1 (GCH1) (packaged within an adeno-associated virus)—into the substantia nigra pars compacta (SNpc) of adolescent animals. We refer to this model as “Enhanced Dopamine in Prodromal Schizophrenia” (EDiPS). We first confirmed that the TH enzyme is preferentially increased in the DS. As adults, EDiPS animals release significantly more DA in the DS following a low dose of amphetamine (AMPH), have increased AMPH-induced hyperlocomotion and show deficits in pre-pulse inhibition (PPI). The glutamatergic response to AMPH is also altered, again in the DS. EDiPS represents an ideal experimental platform to (a) understand how a preferential increase in DA synthesis capacity in the DS relates to “positive” symptoms in schizophrenia; (b) understand how manipulation of DS DA may influence other neurotransmitter systems shown to be altered in patients with schizophrenia; (c) allow researchers to follow an “at risk”-like disease course from adolescence to adulthood; and (d) ultimately allow trials of putative prophylactic agents to prevent disease onset in vulnerable populations.",
author = "Alice Petty and Xiaoying Cui and Yasvir Tesiram and Deniz Kirik and Oliver Howes and Darryl Eyles",
year = "2019",
month = "12",
day = "1",
doi = "10.1038/s41537-019-0074-z",
language = "English",
volume = "5",
journal = "NPJ SCHIZOPHRENIA",
issn = "2334-265X",
publisher = "Nature Publishing Group",
number = "1",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - Enhanced Dopamine in Prodromal Schizophrenia (EDiPS)

T2 - a new animal model of relevance to schizophrenia

AU - Petty, Alice

AU - Cui, Xiaoying

AU - Tesiram, Yasvir

AU - Kirik, Deniz

AU - Howes, Oliver

AU - Eyles, Darryl

PY - 2019/12/1

Y1 - 2019/12/1

N2 - One of the most robust neurochemical abnormalities reported in patients living with schizophrenia is an increase in dopamine (DA) synthesis and release in the dorsal striatum (DS). Importantly, it appears that this increase progresses as a patient transitions from a prodromal stage to the clinical diagnosis of schizophrenia. Here we have recreated this pathophysiology in an animal model by increasing the capacity for DA synthesis preferentially within the DS. To achieve this we administer a genetic construct containing the rate-limiting enzymes in DA synthesis—tyrosine hydroxylase (TH), and GTP cyclohydrolase 1 (GCH1) (packaged within an adeno-associated virus)—into the substantia nigra pars compacta (SNpc) of adolescent animals. We refer to this model as “Enhanced Dopamine in Prodromal Schizophrenia” (EDiPS). We first confirmed that the TH enzyme is preferentially increased in the DS. As adults, EDiPS animals release significantly more DA in the DS following a low dose of amphetamine (AMPH), have increased AMPH-induced hyperlocomotion and show deficits in pre-pulse inhibition (PPI). The glutamatergic response to AMPH is also altered, again in the DS. EDiPS represents an ideal experimental platform to (a) understand how a preferential increase in DA synthesis capacity in the DS relates to “positive” symptoms in schizophrenia; (b) understand how manipulation of DS DA may influence other neurotransmitter systems shown to be altered in patients with schizophrenia; (c) allow researchers to follow an “at risk”-like disease course from adolescence to adulthood; and (d) ultimately allow trials of putative prophylactic agents to prevent disease onset in vulnerable populations.

AB - One of the most robust neurochemical abnormalities reported in patients living with schizophrenia is an increase in dopamine (DA) synthesis and release in the dorsal striatum (DS). Importantly, it appears that this increase progresses as a patient transitions from a prodromal stage to the clinical diagnosis of schizophrenia. Here we have recreated this pathophysiology in an animal model by increasing the capacity for DA synthesis preferentially within the DS. To achieve this we administer a genetic construct containing the rate-limiting enzymes in DA synthesis—tyrosine hydroxylase (TH), and GTP cyclohydrolase 1 (GCH1) (packaged within an adeno-associated virus)—into the substantia nigra pars compacta (SNpc) of adolescent animals. We refer to this model as “Enhanced Dopamine in Prodromal Schizophrenia” (EDiPS). We first confirmed that the TH enzyme is preferentially increased in the DS. As adults, EDiPS animals release significantly more DA in the DS following a low dose of amphetamine (AMPH), have increased AMPH-induced hyperlocomotion and show deficits in pre-pulse inhibition (PPI). The glutamatergic response to AMPH is also altered, again in the DS. EDiPS represents an ideal experimental platform to (a) understand how a preferential increase in DA synthesis capacity in the DS relates to “positive” symptoms in schizophrenia; (b) understand how manipulation of DS DA may influence other neurotransmitter systems shown to be altered in patients with schizophrenia; (c) allow researchers to follow an “at risk”-like disease course from adolescence to adulthood; and (d) ultimately allow trials of putative prophylactic agents to prevent disease onset in vulnerable populations.

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U2 - 10.1038/s41537-019-0074-z

DO - 10.1038/s41537-019-0074-z

M3 - Article

AN - SCOPUS:85063810788

VL - 5

JO - NPJ SCHIZOPHRENIA

JF - NPJ SCHIZOPHRENIA

SN - 2334-265X

IS - 1

M1 - 6

ER -

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