TY - JOUR
T1 - Essential role of NMDA receptor channel ε4 subunit (GluN2D) in the effects of hencyclidine, but not methamphetamine
AU - Hagino, Yoko
AU - Kasai, Shinya
AU - Han, Wenhua
AU - Yamamoto, Hideko
AU - Nabeshima, Toshitaka
AU - Mishina, Masayoshi
AU - Ikeda, Kazutaka
PY - 2010
Y1 - 2010
N2 - Phencyclidine (PCP), a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, increases locomotor activity inrodents and causes schizophrenia-like symptoms in humans. Although activation of the dopamine (DA) pathway is hypothesized to mediate these effects of PCP, the precise mechanisms by which PCP induces its effects remain to be elucidated. The present study investigated the effect of PCP on extracellular levels of DA (DAex) in the striatum and prefrontal cortex (PFC) using in vivo microdialysis in mice lacking the NMDA receptor channel e1 or e4 subunit (GluRε1 [GluN2A] or GluRε4 [GluN2D]) and locomotor activity. PCP significantly increased DAex in wildtype and GluRε1 knockout mice, but not in luRe4 knockout mice, in the striatum and PFC. Acute and repeated administration of PCP did not increase locomotor activity in GluRε4 knockout mice. The present results suggest that PCP enhances dopaminergic transmission and increases locomotor activity by acting at GluRε4.
AB - Phencyclidine (PCP), a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, increases locomotor activity inrodents and causes schizophrenia-like symptoms in humans. Although activation of the dopamine (DA) pathway is hypothesized to mediate these effects of PCP, the precise mechanisms by which PCP induces its effects remain to be elucidated. The present study investigated the effect of PCP on extracellular levels of DA (DAex) in the striatum and prefrontal cortex (PFC) using in vivo microdialysis in mice lacking the NMDA receptor channel e1 or e4 subunit (GluRε1 [GluN2A] or GluRε4 [GluN2D]) and locomotor activity. PCP significantly increased DAex in wildtype and GluRε1 knockout mice, but not in luRe4 knockout mice, in the striatum and PFC. Acute and repeated administration of PCP did not increase locomotor activity in GluRε4 knockout mice. The present results suggest that PCP enhances dopaminergic transmission and increases locomotor activity by acting at GluRε4.
UR - https://www.scopus.com/pages/publications/78149418887
UR - https://www.scopus.com/pages/publications/78149418887#tab=citedBy
U2 - 10.1371/journal.pone.0013722
DO - 10.1371/journal.pone.0013722
M3 - Article
C2 - 21060893
AN - SCOPUS:78149418887
SN - 1932-6203
VL - 5
JO - PloS one
JF - PloS one
IS - 10
M1 - e13722
ER -