A schizophrenia rat model induced by early postnatal phencyclidine treatment and characterized by Magnetic Resonance Imaging

Brian V Broberg; Kristoffer H Madsen; Niels Plath; Christina K Olsen; Birte Y Glenthøj; Olaf B. Paulson; Börje Bjelke; Lise V Søgaard

doi:10.1016/j.bbr.2013.04.026

A schizophrenia rat model induced by early postnatal phencyclidine treatment and characterized by Magnetic Resonance Imaging

Brian V Broberg, Kristoffer H Madsen, Niels Plath, Christina K Olsen, Birte Y Glenthøj, Olaf B. Paulson, Börje Bjelke, Lise V Søgaard

Department of Clinical Medicine

8 Citations (Scopus)

Abstract

Better animal models are needed to aid the development of new medications to alleviate the cognitive deficits associated with schizophrenia. Growing evidence suggests neurodevelopmental insults and disturbances in NMDA receptor (NMDAR) signaling to be involved in the schizophrenia etiology. Acute administration of phencyclidine (PCP) induces schizophrenia-like symptoms in healthy volunteers and exacerbates symptoms in patients with schizophrenia. In this study, pharmacological Magnetic Resonance Imaging (phMRI) was used to evaluate if rats treated with 20. mg/kg PCP on postnatal days 7, 9, and 11 (neoPCP), compared to saline (neoVeh), were hypersensitive to acute PCP administration in adulthood (acutePCP). Intravenous administration of 0.5. mg/kg acutePCP produced robust and sustained relative cerebral blood volume (rCBV) increase in discrete frontal, neocortical, hippocampal, thalamic, and limbic brain structures in both neoPCP:acutePCP and neoVeh:acutePCP rats compared to acute saline treatment (Vehicle control group). AcutePCP injection significantly increased the rCBV response in the medial prefrontal cortex and nucleus accumbens compared to the Vehicle control group, without distinguishing neoPCP and neoVeh animals. However, at late time points (25-33. min post acutePCP injection), neoPCP animals showed significantly higher rCBV values compared to the Vehicle control group, suggesting an altered sensitivity toward NMDAR blockade in adult rats subjected to this neurodevelopmental procedure. In combination with the observed cognitive deficits revealed in this animal model, the present findings indicate that altered NMDAR signaling might underlie the symptomatic changes seen in schizophrenia, adding to the construct and face validity of this model.

Original language	English
Journal	Behavioural Brain Research
Volume	250
Pages (from-to)	1-8
ISSN	0166-4328
DOIs	https://doi.org/10.1016/j.bbr.2013.04.026
Publication status	Published - 1 Aug 2013

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10.1016/j.bbr.2013.04.026

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title = "A schizophrenia rat model induced by early postnatal phencyclidine treatment and characterized by Magnetic Resonance Imaging",

abstract = "Better animal models are needed to aid the development of new medications to alleviate the cognitive deficits associated with schizophrenia. Growing evidence suggests neurodevelopmental insults and disturbances in NMDA receptor (NMDAR) signaling to be involved in the schizophrenia etiology. Acute administration of phencyclidine (PCP) induces schizophrenia-like symptoms in healthy volunteers and exacerbates symptoms in patients with schizophrenia. In this study, pharmacological Magnetic Resonance Imaging (phMRI) was used to evaluate if rats treated with 20. mg/kg PCP on postnatal days 7, 9, and 11 (neoPCP), compared to saline (neoVeh), were hypersensitive to acute PCP administration in adulthood (acutePCP). Intravenous administration of 0.5. mg/kg acutePCP produced robust and sustained relative cerebral blood volume (rCBV) increase in discrete frontal, neocortical, hippocampal, thalamic, and limbic brain structures in both neoPCP:acutePCP and neoVeh:acutePCP rats compared to acute saline treatment (Vehicle control group). AcutePCP injection significantly increased the rCBV response in the medial prefrontal cortex and nucleus accumbens compared to the Vehicle control group, without distinguishing neoPCP and neoVeh animals. However, at late time points (25-33. min post acutePCP injection), neoPCP animals showed significantly higher rCBV values compared to the Vehicle control group, suggesting an altered sensitivity toward NMDAR blockade in adult rats subjected to this neurodevelopmental procedure. In combination with the observed cognitive deficits revealed in this animal model, the present findings indicate that altered NMDAR signaling might underlie the symptomatic changes seen in schizophrenia, adding to the construct and face validity of this model.",

author = "Broberg, {Brian V} and Madsen, {Kristoffer H} and Niels Plath and Olsen, {Christina K} and Glenth{\o}j, {Birte Y} and Paulson, {Olaf B.} and B{\"o}rje Bjelke and S{\o}gaard, {Lise V}",

year = "2013",

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T1 - A schizophrenia rat model induced by early postnatal phencyclidine treatment and characterized by Magnetic Resonance Imaging

AU - Broberg, Brian V

AU - Madsen, Kristoffer H

AU - Plath, Niels

AU - Olsen, Christina K

AU - Glenthøj, Birte Y

AU - Paulson, Olaf B.

AU - Bjelke, Börje

AU - Søgaard, Lise V

PY - 2013/8/1

Y1 - 2013/8/1

N2 - Better animal models are needed to aid the development of new medications to alleviate the cognitive deficits associated with schizophrenia. Growing evidence suggests neurodevelopmental insults and disturbances in NMDA receptor (NMDAR) signaling to be involved in the schizophrenia etiology. Acute administration of phencyclidine (PCP) induces schizophrenia-like symptoms in healthy volunteers and exacerbates symptoms in patients with schizophrenia. In this study, pharmacological Magnetic Resonance Imaging (phMRI) was used to evaluate if rats treated with 20. mg/kg PCP on postnatal days 7, 9, and 11 (neoPCP), compared to saline (neoVeh), were hypersensitive to acute PCP administration in adulthood (acutePCP). Intravenous administration of 0.5. mg/kg acutePCP produced robust and sustained relative cerebral blood volume (rCBV) increase in discrete frontal, neocortical, hippocampal, thalamic, and limbic brain structures in both neoPCP:acutePCP and neoVeh:acutePCP rats compared to acute saline treatment (Vehicle control group). AcutePCP injection significantly increased the rCBV response in the medial prefrontal cortex and nucleus accumbens compared to the Vehicle control group, without distinguishing neoPCP and neoVeh animals. However, at late time points (25-33. min post acutePCP injection), neoPCP animals showed significantly higher rCBV values compared to the Vehicle control group, suggesting an altered sensitivity toward NMDAR blockade in adult rats subjected to this neurodevelopmental procedure. In combination with the observed cognitive deficits revealed in this animal model, the present findings indicate that altered NMDAR signaling might underlie the symptomatic changes seen in schizophrenia, adding to the construct and face validity of this model.

AB - Better animal models are needed to aid the development of new medications to alleviate the cognitive deficits associated with schizophrenia. Growing evidence suggests neurodevelopmental insults and disturbances in NMDA receptor (NMDAR) signaling to be involved in the schizophrenia etiology. Acute administration of phencyclidine (PCP) induces schizophrenia-like symptoms in healthy volunteers and exacerbates symptoms in patients with schizophrenia. In this study, pharmacological Magnetic Resonance Imaging (phMRI) was used to evaluate if rats treated with 20. mg/kg PCP on postnatal days 7, 9, and 11 (neoPCP), compared to saline (neoVeh), were hypersensitive to acute PCP administration in adulthood (acutePCP). Intravenous administration of 0.5. mg/kg acutePCP produced robust and sustained relative cerebral blood volume (rCBV) increase in discrete frontal, neocortical, hippocampal, thalamic, and limbic brain structures in both neoPCP:acutePCP and neoVeh:acutePCP rats compared to acute saline treatment (Vehicle control group). AcutePCP injection significantly increased the rCBV response in the medial prefrontal cortex and nucleus accumbens compared to the Vehicle control group, without distinguishing neoPCP and neoVeh animals. However, at late time points (25-33. min post acutePCP injection), neoPCP animals showed significantly higher rCBV values compared to the Vehicle control group, suggesting an altered sensitivity toward NMDAR blockade in adult rats subjected to this neurodevelopmental procedure. In combination with the observed cognitive deficits revealed in this animal model, the present findings indicate that altered NMDAR signaling might underlie the symptomatic changes seen in schizophrenia, adding to the construct and face validity of this model.

U2 - 10.1016/j.bbr.2013.04.026

DO - 10.1016/j.bbr.2013.04.026

M3 - Journal article

C2 - 23644161

SN - 0166-4328

VL - 250

SP - 1

EP - 8

JO - Behavioural Brain Research

JF - Behavioural Brain Research

ER -

A schizophrenia rat model induced by early postnatal phencyclidine treatment and characterized by Magnetic Resonance Imaging

Abstract

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