Sustained N-methyl-d-aspartate receptor hypofunction remodels the dopamine system and impairs phasic signaling. / Ferris, MJ; Milenkovic, M; Liu, S; Mielnik, CA; Beerepoot, P; John, CE; España, RA; Sotnikova, TD; Gainetdinov, RR; Borgland, SL; Jones, SR; Ramsey, AJ.
In: European Journal of Neuroscience, 2014.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Sustained N-methyl-d-aspartate receptor hypofunction remodels the dopamine system and impairs phasic signaling.
AU - Ferris, MJ
AU - Milenkovic, M
AU - Liu, S
AU - Mielnik, CA
AU - Beerepoot, P
AU - John, CE
AU - España, RA
AU - Sotnikova, TD
AU - Gainetdinov, RR
AU - Borgland, SL
AU - Jones, SR
AU - Ramsey, AJ.
PY - 2014
Y1 - 2014
N2 - Chronic N-methyl-d-aspartate receptor (NMDAR) hypofunction has been proposed as a contributing factor to symptoms of schizophrenia. However, it is unclear how sustained NMDAR hypofunction throughout development affects other neurotransmitter systems that have been implicated in the disease. Dopamine neuron biochemistry and activity were examined to determine whether sustained NMDAR hypofunction causes a state of hyperdopaminergia. We report that a global, genetic reduction in NMDARs led to a remodeling of dopamine neurons, substantially affecting two key regulators of dopamine homeostasis, i.e., tyrosine hydroxylase and the dopamine transporter. In NR1 knockdown mice, dopamine synthesis and release were attenuated, and dopamine clearance was increased. Although these changes would have the effect of reducing dopamine transmission, we demonstrated that a state of hyperdopaminergia existed in these mice because dopamine D2 autoreceptors were desensitized. In support of this conclusion, NR1 knockdown dopamine ne
AB - Chronic N-methyl-d-aspartate receptor (NMDAR) hypofunction has been proposed as a contributing factor to symptoms of schizophrenia. However, it is unclear how sustained NMDAR hypofunction throughout development affects other neurotransmitter systems that have been implicated in the disease. Dopamine neuron biochemistry and activity were examined to determine whether sustained NMDAR hypofunction causes a state of hyperdopaminergia. We report that a global, genetic reduction in NMDARs led to a remodeling of dopamine neurons, substantially affecting two key regulators of dopamine homeostasis, i.e., tyrosine hydroxylase and the dopamine transporter. In NR1 knockdown mice, dopamine synthesis and release were attenuated, and dopamine clearance was increased. Although these changes would have the effect of reducing dopamine transmission, we demonstrated that a state of hyperdopaminergia existed in these mice because dopamine D2 autoreceptors were desensitized. In support of this conclusion, NR1 knockdown dopamine ne
M3 - статья
JO - European Journal of Neuroscience
JF - European Journal of Neuroscience
SN - 0953-816X
ER -
ID: 5835472