Increased rewarding properties of morphine in dopamine-transporter knockout mice

被引:72
|
作者
Spielewoy, C
Gonon, F
Roubert, C
Fauchey, V
Jaber, M
Caron, MG
Roques, BP
Hamon, M
Betancur, C
Maldonado, R
Giros, B
机构
[1] INSERM, U513, F-94100 Creteil, France
[2] INSERM, U288, F-75013 Paris, France
[3] Univ Bordeaux 2, CNRS, UMR 5541, F-33076 Bordeaux, France
[4] Duke Univ, Med Ctr, Howard Hughes Med Inst Lab, Dept Cell Biol, Durham, NC 27710 USA
[5] Duke Univ, Med Ctr, Howard Hughes Med Inst Lab, Dept Med, Durham, NC 27710 USA
[6] INSERM, U266, F-75006 Paris, France
[7] Univ Pompeu Fabra, Dept Neuropharmacol, Barcelona 08003, Spain
关键词
c-fos expression; conditioned place preference; in vivo voltammetry; locomotion; morphine withdrawal;
D O I
10.1046/j.1460-9568.2000.00063.x
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The activation of dopamine (DA) neurotransmission plays a crucial role in the behavioural responses to drugs of abuse. In particular, increased extracellular levels of DA within the mesolimbic pathway have been implicated in the rewarding and locomotor stimulatory properties of morphine. We investigated the behavioural responses to morphine in mice with a genetic disruption of the DA transporter (DAT), resulting in a constitutively high level of extrasynaptic DA. In the conditioned place preference test, DAT(-/-) mice exhibited a stronger rewarding response to morphine (5 mg/kg, s.c.) compared with control littermates. However, the same dose of morphine failed to increase locomotor activity in DAT(-/-) mice, whilst enhancing locomotion in DAT(+/-) and DAT(+/+) animals. Morphine-induced analgesia was unaffected in mutant mice, but the behavioural expression of naloxone-induced withdrawal signs was blunted. In vivo voltammetry in the shell of the nucleus accumbens revealed that morphine was able to stimulate DA neurons in DAT(-/-) mice, resulting in the accumulation of higher extracellular DA levels compared with control animals. Morphine also induced a higher rate of c-fos transcription in the shell of the nucleus accumbens in mutant mice. We conclude that morphine-induced rewarding responses are firmly established in DAT mutant mice despite a DA transmission that is already tonically activated, and independently of any effect on locomotion. These particular behavioural responses to morphine may be associated with the action of the drug on DA release and c-fos expression in the shell of the nucleus accumbens of DAT(-/-) mice.
引用
收藏
页码:1827 / 1837
页数:11
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