Mice lacking dopamine D4 receptors are supersensitive to ethanol, cocaine, and methamphetamine

被引：382

作者：

Rubinstein, M

Phillips, TJ

Bunzow, JR

Falzone, TL

Dziewczapolski, G

Zhang, G

Fang, Y

Larson, JL

McDougall, JA

Chester, JA

Saez, C

Pugsley, TA

Gershanik, O

Low, MJ

Grandy, DK

机构：

[1] OREGON HLTH SCI UNIV,VOLLUM INST,PORTLAND,OR 97201

[2] OREGON HLTH SCI UNIV,DEPT BEHAV NEUROSCI,PORTLAND,OR 97201

[3] OREGON HLTH SCI UNIV,DEPT CELL & DEV BIOL,PORTLAND,OR 97201

[4] UNIV BUENOS AIRES,INST INVEST FARMACOL,RA-1053 BUENOS AIRES,DF,ARGENTINA

[5] UNIV BUENOS AIRES,INST INVEST INGN GENET & BIOL MOL,CONICET,RA-1053 BUENOS AIRES,DF,ARGENTINA

[6] UNIV BUENOS AIRES,DEPT QUIM BIOL,FCEYN,RA-1053 BUENOS AIRES,DF,ARGENTINA

[7] DEPT VET AFFAIRS MED CTR,RES SERV,PORTLAND,OR 97201

[8] HOSP UNIV VIRGEN DEL ROCIO,SEVILLE 41013,SPAIN

[9] WARNER LAMBERT PARKE DAVIS,PARKE DAVIS PHARMACEUT RES,ANN ARBOR,MI 48105

来源：

CELL | 1997年 / 90卷 / 06期

关键词：

D O I：

10.1016/S0092-8674(00)80365-7

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The human dopamine D4 receptor (D4R) has received considerable attention because of its high affinity for the atypical antipsychotic clozapine and the unusually polymorphic nature of its gene. To clarify the in vivo role of the D4R, we produced and analyzed mutant mice (D4R(-/-)) lacking this protein. Although less active in open field tests, D4R(-/-) mice outperformed wildtype mice on the rotarod and displayed locomotor supersensitivity to ethanol, cocaine, and methamphetamine. Biochemical analyses revealed that dopamine synthesis and its conversion to DOPAC were elevated in the dorsal striatum from D4R(-/-) mice. Based on these findings, we propose that the D4R modulates normal, coordinated and drug-stimulated motor behaviors as well as the activity of nigrostriatal dopamine neurons.

引用

页码：991 / 1001

页数：11

共 59 条

[1] A targeted mutation of the D-3 dopamine receptor gene is associated with hyperactivity in mice [J].