The uncompetitive NMDA receptor antagonists ketamine and memantine preferentially increase the choice for a small, immediate reward in low-impulsive rats.
The uncompetitive NMDA receptor antagonists ketamine and memantine preferentially increase the choice for a small, immediate reward in low-impulsive rats.
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DOI：
10.1007/s00213-012-2898-3
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发表时间：
2013-03
影响因子：
3.4
通讯作者：
Sabino, Valentina
中科院分区：
文献类型：
--
作者：
Cottone, Pietro;Iemolo, Attilio;Narayan, Aditi R.;Kwak, Jina;Momaney, Duncan;Sabino, Valentina
关键词：
冲动行为可以分为冲动行为和冲动选择，前者是无法抑制做出反应的冲动行为，后者是更倾向于立即获得更小的奖励，而不是延迟获得更有利的奖励。虽然N-甲基-D-天冬氨酸（NMDA）受体拮抗剂对冲动行为的影响已被广泛表征，但关于这类药物对冲动选择的影响的报道很少且相互矛盾。采用改进的调节延迟任务，我们研究了非竞争性和竞争性阻断NMDA受体对冲动选择的影响。雄性Wistar大鼠在一个修改后的调整延迟任务，其中包括重复选择之间的低强化立即交付的解决方案和高度强化后交付的解决方案的可变延迟。然后给大鼠施用NMDA受体非竞争性拮抗剂氯胺酮或美金刚，或竞争性拮抗剂D-AP-5或CGS 19755。氯胺酮治疗剂量依赖性地增加冲动的选择，这种效果是选择性的低冲动，但不高冲动的大鼠。同样，美金刚治疗剂量依赖性地增加了冲动的选择与低冲动大鼠的优先效应。虽然D-AP-5治疗不影响冲动选择，但CGS 19755增加了冲动性，然而，在相同剂量下，它引起了显着的反应抑制。NMDA受体非竞争性，但不是竞争性的，拮抗剂显着增加冲动的选择，优先在低冲动大鼠。这些发现表明，NMDA受体阻滞剂对冲动选择的影响是不可推广的，并取决于所用拮抗剂的具体作用机制。
Impulsive behavior is categorically differentiated between impulsive action, the inability to withhold from acting out a response, and impulsive choice, the greater preference for an immediate and smaller reward over a delayed but more advantageous reward. While the effects of N-methyl-D-aspartic acid (NMDA) receptor antagonists on impulsive action have been extensively characterized, there are very few and conflicting reports on the effects of this class of drugs on impulsive choice. Using a modified adjusting delay task, we investigated the effects of uncompetitive and competitive blockade of NMDA receptors on impulsive choice. Male Wistar rats were trained in a modified adjusting delay task, which involved repeated choice between a low reinforcing solution delivered immediately and a highly reinforcing solution delivered after a variable delay. Rats were then administered either the NMDA receptor uncompetitive antagonists ketamine or memantine, or the competitive antagonists D-AP-5 or CGS 19755. Ketamine treatment dose-dependently increased impulsive choice, and this effect was selective for low-impulsive but not high-impulsive rats. Similarly, memantine treatment dose-dependently increased impulsive choice with a preferential effect for low-impulsive rats. While D-AP-5 treatment did not affect impulsive choice, CGS 19755 increased impulsivity, however, at the same doses at which it caused a marked response inhibition. NMDA receptor uncompetitive, but not competitive, antagonists significantly increased impulsive choice, preferentially in low-impulsive rats. These findings demonstrate that the effects of NMDA receptor blockade on impulsive choice are not generalizable and depend on the specific mechanism of action of the antagonist used.
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影响因子：
3.4
作者：
Blasio, Angelo;Narayan, Aditi R.;Kaminski, Barbara J.;Steardo, Luca;Sabino, Valentina;Cottone, Pietro
通讯作者：
Cottone, Pietro
DOI：
10.1124/jpet.108.143370
发表时间：
2008-12-01
影响因子：
3.5
作者：
Ardayfio, Paul A.;Benvenga, Mark J.;Marek, Gerard J.
通讯作者：
Marek, Gerard J.
影响因子：
11
作者：
Adams, J;Crosbie, J;Barr, CL
通讯作者：
Barr, CL
影响因子：
5
作者：
Ebert, B;Mikkelsen, S;Borgbjerg, FM
通讯作者：
Borgbjerg, FM
影响因子：
2.5
作者：
Blanpied, TA;Boeckman, FA;Johnson, JW
通讯作者：
Johnson, JW