TY - JOUR
T1 - Similarities in the behavior and molecular deficits in the frontal cortex between the neurotensin receptor subtype 1 knockout mice and chronic phencyclidine-treated mice
T2 - Relevance to schizophrenia
AU - Li, Zhimin
AU - Boules, Mona
AU - Williams, Katrina
AU - Gordillo, Andres
AU - Li, Shuhua
AU - Richelson, Elliott
N1 - Funding Information:
This work was supported by NIMH grant MH71241 .
PY - 2010/11
Y1 - 2010/11
N2 - Much evidence suggests that targeting the neurotensin (NT) system may provide a novel and promising treatment for schizophrenia. Our recent work shows that: NTS1 knockout (NTS1-/-) mice may provide a potential animal model for studying schizophrenia by investigating the effect of deletion NTS1 receptor on amphetamine-induced hyperactivity and neurochemical changes. The data indicate a hyper-dopaminergic state similar to the excessive striatal DA activity reported in schizophrenia. The present study was done to determine if NTS1-/- mice also have similar changes in behavior, in prefrontal neurotransmitters, and in protein expression, as observed in wild type (WT) mice treated with the psychotomimetic phencylclidine (PCP), an animal model for schizophrenia. Our results showed many similarities between untreated NTS1-/- mice and WT mice chronically treated with PCP (as compared with untreated WT mice): 1) lower PCP-induced locomotor activity; 2) similar avolition-like behavior in forced-swim test and tail suspension test; 3) lower prefrontal glutamate levels; 4) less PCP-induced dopamine release in medial prefrontal cortex (mPFC); and 5) down-regulation of mRNA and protein for DA D1, DA D2, and NMDAR2A in mPFC. Therefore, these data strengthen the hypothesis that the NTS1-/- mouse is an animal model of schizophrenia, particularly for the dysfunction of the prefrontal cortex. In addition, after chronic PCP administration, the DA D1 receptor was up-regulated in NTS1-/- mice, results which suggest a possible interaction of NTS1/DA D1 in mPFC contributing to chronic PCP-induced schizophrenia-like signs.
AB - Much evidence suggests that targeting the neurotensin (NT) system may provide a novel and promising treatment for schizophrenia. Our recent work shows that: NTS1 knockout (NTS1-/-) mice may provide a potential animal model for studying schizophrenia by investigating the effect of deletion NTS1 receptor on amphetamine-induced hyperactivity and neurochemical changes. The data indicate a hyper-dopaminergic state similar to the excessive striatal DA activity reported in schizophrenia. The present study was done to determine if NTS1-/- mice also have similar changes in behavior, in prefrontal neurotransmitters, and in protein expression, as observed in wild type (WT) mice treated with the psychotomimetic phencylclidine (PCP), an animal model for schizophrenia. Our results showed many similarities between untreated NTS1-/- mice and WT mice chronically treated with PCP (as compared with untreated WT mice): 1) lower PCP-induced locomotor activity; 2) similar avolition-like behavior in forced-swim test and tail suspension test; 3) lower prefrontal glutamate levels; 4) less PCP-induced dopamine release in medial prefrontal cortex (mPFC); and 5) down-regulation of mRNA and protein for DA D1, DA D2, and NMDAR2A in mPFC. Therefore, these data strengthen the hypothesis that the NTS1-/- mouse is an animal model of schizophrenia, particularly for the dysfunction of the prefrontal cortex. In addition, after chronic PCP administration, the DA D1 receptor was up-regulated in NTS1-/- mice, results which suggest a possible interaction of NTS1/DA D1 in mPFC contributing to chronic PCP-induced schizophrenia-like signs.
KW - Dopamine
KW - Glutamate
KW - Neurotensin receptor
KW - Phencyclidine
KW - Prefrontal cortex
KW - Schizophrenia
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U2 - 10.1016/j.nbd.2010.07.011
DO - 10.1016/j.nbd.2010.07.011
M3 - Article
C2 - 20659557
AN - SCOPUS:78650835626
SN - 0969-9961
VL - 40
SP - 467
EP - 477
JO - Neurobiology of Disease
JF - Neurobiology of Disease
IS - 2
ER -