TY - JOUR
T1 - Dopamine D3 receptor blockade rescues hyper-dopamine activity-induced deficit in novel object recognition memory
AU - Chang, Pi Kai
AU - Yu, Lung
AU - Chen, Jin Chung
N1 - Publisher Copyright:
© 2018
PY - 2018/5/1
Y1 - 2018/5/1
N2 - Patients afflicted with bipolar disorder demonstrate significant impairments in recognition and episodic memory during acute depressive and manic episodes. These impairments and the related pathophysiology may result from over-activation of the brain dopamine (DA) system. In order to model overactive DA transmission in a well-established novel object recognition (NOR) memory test, we used DA transporter knockdown (DAT-KD) mice, which exhibit reduced DAT expression and display hyper-dopaminergic phenotypes. DAT-KD mice exhibited impaired NOR memory compared to wild-type (WT) mice. This impairment was prevented by administration of FAUC365, a DA D3 receptor (D3R) selective antagonist, prior to object learning. Similarly, D3R knockout (KO)/DAT-KD double mutant mice displayed performance in the NOR test that was comparable to WT mice, suggesting that deficiencies in NOR performance in DAT-KD mice can be compensated by diminishing D3R signaling. GBR12909, a DAT blocker, also impaired NOR performance in WT mice, but not in D3R KO mice. Impaired NOR performance in GBR12909-treated WT mice was also prevented by pretreatment with FAUC365. Together, these findings indicate that reduced DAT activity can impair recognition memory in the NOR test, and D3R appears to be necessary to mediate this effect.
AB - Patients afflicted with bipolar disorder demonstrate significant impairments in recognition and episodic memory during acute depressive and manic episodes. These impairments and the related pathophysiology may result from over-activation of the brain dopamine (DA) system. In order to model overactive DA transmission in a well-established novel object recognition (NOR) memory test, we used DA transporter knockdown (DAT-KD) mice, which exhibit reduced DAT expression and display hyper-dopaminergic phenotypes. DAT-KD mice exhibited impaired NOR memory compared to wild-type (WT) mice. This impairment was prevented by administration of FAUC365, a DA D3 receptor (D3R) selective antagonist, prior to object learning. Similarly, D3R knockout (KO)/DAT-KD double mutant mice displayed performance in the NOR test that was comparable to WT mice, suggesting that deficiencies in NOR performance in DAT-KD mice can be compensated by diminishing D3R signaling. GBR12909, a DAT blocker, also impaired NOR performance in WT mice, but not in D3R KO mice. Impaired NOR performance in GBR12909-treated WT mice was also prevented by pretreatment with FAUC365. Together, these findings indicate that reduced DAT activity can impair recognition memory in the NOR test, and D3R appears to be necessary to mediate this effect.
KW - Dopamine D3 receptor
KW - Dopamine transporter
KW - Novel object recognition
UR - http://www.scopus.com/inward/record.url?scp=85041689879&partnerID=8YFLogxK
U2 - 10.1016/j.neuropharm.2018.01.046
DO - 10.1016/j.neuropharm.2018.01.046
M3 - 文章
C2 - 29407766
AN - SCOPUS:85041689879
SN - 0028-3908
VL - 133
SP - 216
EP - 223
JO - Neuropharmacology
JF - Neuropharmacology
ER -