Involvement of Glutamate NMDA Receptors in the Acute, Long-Term, and Conditioned Effects of Amphetamine on Rat 50 kHz Ultrasonic Vocalizations.
Involvement of Glutamate NMDA Receptors in the Acute, Long-Term, and Conditioned Effects of Amphetamine on Rat 50 kHz Ultrasonic Vocalizations.
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DOI：
10.1093/ijnp/pyv057
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发表时间：
2015-05-19
期刊：
影响因子：
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通讯作者：
Simola N
中科院分区：
文献类型：
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作者：
Costa G;Morelli M;Simola N
大鼠在自然或药理愉悦刺激下发出50 kHz超声发声（USVs），这些USVs已成为研究药物激励特性的新行为测量方法。早期研究表明，多巴胺能系统的激活与50 kHz USV发射密切相关。然而，也有证据表明，非多巴胺能神经递质参与这种行为反应。为了确定谷氨酸传输是否在苯丙胺刺激的50 kHz USV发射中起作用，大鼠接受5个苯丙胺（1- 2 mg/kg，i. p.）在试验笼中隔日给药，单独或与谷氨酸N-甲基-D-天冬氨酸受体拮抗剂MK-801（0.1-0.5mg/kg，i. p.）组合。给药停止后7天，将大鼠重新暴露于试验笼中以评估药物调节，然后接受药物激发。评价USV和运动活性，沿着不同脑区域中Zif-268的免疫荧光和Y迷宫中的自发交替。安非他明治疗的大鼠表现出更高的50 kHz USV的排放量和自发活动比车辆治疗的大鼠，并发出条件发声测试笼重新曝光。与安非他明处理的大鼠相比，在重复处理和激发期间，安非他明和MK-801联合给药的大鼠显示出较低且呈剂量依赖性的50 kHz USV发射，但运动活动并未降低，并且条件性发声很少。这些影响与安非他明攻击后Zif-268水平较低和自发交替缺陷有关。这些结果表明，谷氨酸传输参与急性，长期和条件作用的安非他明对50 kHz的USVs，可能通过影响安非他明诱导的长期神经元的变化和/或安非他明相关的记忆。
Rats emit 50kHz ultrasonic vocalizations (USVs) in response to either natural or pharmacological pleasurable stimuli, and these USVs have emerged as a new behavioral measure for investigating the motivational properties of drugs. Earlier studies have indicated that activation of the dopaminergic system is critically involved in 50kHz USV emissions. However, evidence also exists that non-dopaminergic neurotransmitters participate in this behavioral response. To ascertain whether glutamate transmission plays a role in 50kHz USV emissions stimulated by amphetamine, rats received five amphetamine (1–2mg/kg, i.p.) administrations on alternate days in a test cage, either alone or combined with the glutamate N-methyl-D-aspartate receptor antagonist MK-801 (0.1–0.5mg/kg, i.p.). Seven days after treatment discontinuation, rats were re-exposed to the test cage to assess drug conditioning, and afterwards received a drug challenge. USVs and locomotor activity were evaluated, along with immunofluorescence for Zif-268 in various brain regions and spontaneous alternation in a Y maze. Amphetamine-treated rats displayed higher 50kHz USV emissions and locomotor activity than vehicle-treated rats, and emitted conditioned vocalizations on test cage re-exposure. Rats co-administered amphetamine and MK-801 displayed lower and dose-dependent 50kHz USV emissions, but not lower locomotor activity, during repeated treatment and challenge, and scarce conditioned vocalization compared with amphetamine-treated rats. These effects were associated with lower levels of Zif-268 after amphetamine challenge and spontaneous alternation deficits. These results indicate that glutamate transmission participates in the acute, long-term, and conditioned effects of amphetamine on 50kHz USVs, possibly by influencing amphetamine-induced long-term neuronal changes and/or amphetamine-associated memories.