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首页> 外文期刊>The European Journal of Neuroscience >Behavioural adaptations to addictive drugs in mice lacking the NMDA receptor epsilon1 subunit.
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Behavioural adaptations to addictive drugs in mice lacking the NMDA receptor epsilon1 subunit.

机译：缺少NMDA受体epsilon1亚基的小鼠对成瘾药物的行为适应。

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摘要

N-methyl-D-aspartate (NMDA) receptors, a subtype of glutamate receptors (GluRs) formed by assembly of the GluRzeta subunit (called NR1 in rats) with any one of four GluRepsilon subunits (GluRepsilon1-4; NR2A-D), play an important role in excitatory neurotransmission, synaptic plasticity and brain development. Recent pharmacological studies have also indicated a role for NMDA receptors in drug addiction. In the present study, we investigated the behavioural adaptations to addictive drugs such as phencyclidine (PCP), methamphetamine (MAP) and morphine (MOR) in mice lacking the GluRepsilon1 subunit of the NMDA receptor. GluRepsilon1 mutant mice exhibited a malfunction of NMDA receptors, as evidenced by the reduction of [3H]MK-801 binding in an autoradiographic receptor binding assay. GluRepsilon1 mutant mice showed an attenuation of acute PCP- and MAP-induced hyperlocomotion. The development of sensitization by repeated treatment with PCP and MAP at a low, but not high, dose was also suppressed. The development of MOR-induced analgesic tolerance and naloxone-precipitated MOR withdrawal symptoms were attenuated in GluRepsilon1 mutant mice. In the place conditioning test, PCP-induced place aversion in naive mice and place preference in PCP-pretreated mice, as well as MOR-induced place preference, were diminished whereas MAP-induced place preference was not affected in GluRepsilon1 mutant mice. These findings provide genetic evidence that GluRepsilon1 subunit-containing NMDA receptors are involved in certain aspects of drug addiction.
机译：N-甲基-D-天冬氨酸（NMDA）受体，一种谷氨酸受体（GluR）的亚型，是通过将GluRzeta亚基（在大鼠中称为NR1）与四个GluRepsilon亚基（GluRepsilon1-4; NR2A-D）组装而成的，在兴奋性神经传递，突触可塑性和大脑发育中起重要作用。最近的药理研究还表明，NMDA受体在成瘾中起着作用。在本研究中，我们调查了缺少NMDA受体GluRepsilon1亚基的小鼠对成瘾药物如苯环利定（PCP），甲基苯丙胺（MAP）和吗啡（MOR）的行为适应性。 GluRepsilon1突变小鼠表现出NMDA受体的功能异常，这通过放射自显影受体结合试验中[3H] MK-801结合的减少得以证明。 GluRepsilon1突变小鼠显示出急性PCP和MAP诱导的运动过度减弱。在低剂量但非高剂量下，用PCP和MAP重复治疗引起的敏化现象也得到了抑制。在GluRepsilon1突变小鼠中，MOR诱导的镇痛耐受性的发展和纳洛酮沉淀的MOR戒断症状减弱。在位置条件测试中，PCP诱导的天真小鼠厌恶和PCP预处理小鼠的位置偏好以及MOR诱导的位置偏好均降低，而MAP诱导的位置偏好在GluRepsilon1突变小鼠中不受影响。这些发现提供了遗传证据，证明含有GluRepsilon1亚基的NMDA受体与药物成瘾的某些方面有关。

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