Ontogeny of dopamine agonist-induced sensitization: Role of NMDA receptors
Ontogeny of dopamine agonist-induced sensitization: Role of NMDA receptors
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DOI：
10.1007/s002130050175
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发表时间：
1997-01-01
影响因子：
3.4
通讯作者：
McDougall, SA
中科院分区：
文献类型：
--
作者：
Duke, MA;ONeal, J;McDougall, SA
与成人相比，断奶前大鼠在停止多巴胺（DA）激动剂治疗后仅几天表现出行为致敏。这种个体发生差异的原因尚不清楚，但n -甲基- d -天冬氨酸（NMDA）受体的成熟变化可能是原因，因为刺激这些受体是DA激动剂诱导的成年大鼠致敏的必要条件。本研究的目的是研究NMDA受体功能与DA激动剂诱导的断奶前致敏之间的关系。为此，17日龄大鼠连续4天注射生理盐水或0.3 mg/kg地佐西平（一种非竞争性NMDA受体拮抗剂），30分钟后注射生理盐水、2.5 mg/kg安非他明（一种间接DA激动剂）或1.0 mg/kg NPA（一种直接DA激动剂）。2天后（即22日龄）测试致敏性，大鼠接受生理盐水、安非他明、NPA或二唑西平的激发注射。结果表明，NMDA拮抗剂对断奶前大鼠的行为致敏具有成体样的作用，因为苯丙胺和npa诱导的致敏被二唑西平预处理消除。单独给药时，二唑西平显著增加了断奶前大鼠的运动活动（即交叉线），这种效果在反复给药后变得敏感。最后，已经对二氯西平过敏的断奶前大鼠对安非他明或NPA没有交叉致敏。因此，除了少数例外，NMDA受体刺激似乎以类似的方式调节整个个体发生的致敏性。这一发现表明，NMDA受体系统的成熟差异并不是年轻动物缺乏长期致敏的原因。
In contrast to adults, preweanling rats exhibit behavioral sensitization for only a few days after cessation of dopamine (DA) agonist treatment. The reasons for this ontogenetic difference are uncertain, but maturational changes in the N-methyl-D-aspartate (NMDA) receptor may be responsible, since stimulation of these receptors is necessary for the development of DA agonist-induced sensitization in adult rats. The purpose of the present study was to examine the relationship between NMDA receptor functioning and DA agonist-induced sensitization during the preweanling period. To that end, 17-day-old rats were injected (IP) on 4 consecutive days with saline or 0.3 mg/kg dizocilpine (a non-competitive NMDA receptor antagonist) followed, 30 min later, by an injection of saline, 2.5 mg/kg amphetamine (an indirect DA agonist), or 1.0 mg/kg NPA (a direct DA agonist). Sensitization was tested 2 days later (i.e., at 22 days of age), with rats receiving a challenge injection of saline, amphetamine, NPA, or dizocilpine. Results showed that the NMDA antagonist had adult-like effects on the behavioral sensitization of preweanling rats, as amphetamine-and NPA-induced sensitization were eliminated by dizocilpine pretreatment. When given alone, dizocilpine substantially increased the locomotor activity (i.e., line-crosses) of preweanling rats, an effect that became sensitized with repeated drug treatment. Lastly, preweanling rats already sensitized to dizocilpine did not exhibit cross-sensitization to amphetamine or NPA. Thus, with few exceptions, NMDA receptor stimulation appears to modulate sensitization in a similar fashion across ontogeny. This finding suggests that maturational differences in the NMDA receptor system are not responsible for the lack of long-term sensitization in the younger animal.