Sensitization of prepulse inhibition deficits by repeated administration of dizocilpine
Sensitization of prepulse inhibition deficits by repeated administration of dizocilpine
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DOI：
10.1007/s002130100776
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发表时间：
2001-06
影响因子：
3.4
通讯作者：
Brigitte Schulz;M. Fendt;V. Pedersen;M. Koch
中科院分区：
文献类型：
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作者：
Brigitte Schulz;M. Fendt;V. Pedersen;M. Koch
理由：重复施用精神活性药物会导致这些化合物的行为效应逐渐增强，这种现象称为敏化。目的：我们测试了重复施用非竞争性 NMDA 受体拮抗剂地佐西平 (MK-801) 是否会诱导该化合物对前脉冲抑制 (PPI) 的破坏作用的敏化。 方法：大鼠每天在惊跳笼中接受 9 次腹腔注射 0.1 mg/kg MK-801，并在惊跳笼中测试 PPI、无前脉冲情况下的惊跳和运动活动。另一组大鼠在笼子里接受 MK-801 治疗 9 天，但没有进行日常测试。对照组每天注射生理盐水并进行测试，而另一组大鼠则在笼子里注射生理盐水，但不进行每日测试。第10天，所有大鼠均接受盐水注射并进行测试。第 11 天，所有大鼠均注射 0.1 mg/kg MK-801 并再次进行测试。第 12 天，所有大鼠均接受 1 mg/kgdl-安非他明 IP 注射，并进行 PPI 测试，以评估可能的交叉致敏作用。结果：MK-801 在测试的第 1 天没有影响，但在 6-9 天的每日治疗和测试后，在惊吓笼中接受药物但在家庭笼中接受药物的大鼠中，MK-801 诱导 PPI 缺乏。经过反复治疗和测试后，运动活动有所增加。在这些大鼠中，MK-801 也存在增强惊吓程度的敏化趋势。在惊吓笼中每天注射 MK-801 的大鼠中，dl-安非他明降低了 PPI，其程度与注射盐水相似。结论：由于 PPI 被认为是感觉运动门控的一种测量方法，我们的数据表明，由 MK-801 经过敏化过程。这些发现可能与当前将精神分裂症症状与致敏相关的假设相关。
Rationale:Repeated administration of psychoactive drugs results in a progressive enhancement of the behavioral effects of these compounds, a phenomenon termed sensitization.Objective:We tested whether repeated administration of the non-competitive NMDA receptor antagonist dizocilpine (MK-801) induces sensitization of the disruptive effects of this compound on prepulse inhibition (PPI) of startle.Methods:Rats received nine daily IP injections of 0.1 mg/kg MK-801 in the startle cage and were tested for PPI, startle in the absence of prepulses and motor activity in the startle cage. Another group of rats received MK-801 in the home cage on 9 days without daily testing. Controls were injected with saline and tested daily, while a separate group of rats received saline in the home cage without daily testing. On day 10, all rats received saline injections and were tested. On day 11, all rats were injected with 0.1 mg/kg MK-801 and tested again. On day 12, all rats received 1 mg/kgdl-amphetamine IP and were tested for PPI, to assess a possible cross-sensitization.Results:MK-801 had no effect on day 1 of testing but induced a PPI deficit after 6–9 days of daily treatment and testing in those rats that received the drug in the startle cage, but not in the home cage. Motor activity was increased after repeated treatment and testing. There was also a trend towards sensitization of enhancement of the startle magnitude by MK-801 in these rats.dl-Amphetamine reduced PPI in those rats that received daily MK-801 injections in the startle cage to a similar extent as saline injections.Conclusions:Since PPI is considered as a measure of sensorimotor gating, our data indicate that sensorimotor gating deficits induced by MK-801 are subject to a sensitization process. These findings may be relevant for current hypotheses relating schizophrenic symptoms to sensitization.