Akiyama K, Ujike H, Sakai K, Shimizu Y, Kodama M, Kuroda S
Department of Neuropsychiatry, Okayama University Medical School, Japan.
Pharmacol Biochem Behav. 1998 Dec;61(4):419-26. doi: 10.1016/s0091-3057(98)00121-x.
The present study investigated the effect of pretreatment with 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX), an alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, on behavioral sensitization induced by methamphetamine (METH) and cocaine at doses that are transitional relative to the induction of an acute response of locomotion and interrupting episodes of sniffing and head movement. Male Sprague-Dawley rats were randomly assigned to four groups that received daily either 20 mg/kg NBQX + 3 mg/kg METH, 40 mg/kg NBQX + 3 mg/kg METH, vehicle + 3 mg/kg METH, or vehicle + saline daily for 10 days. In another experiment, rats of four groups received daily either 20 mg/kg NBQX + 15 mg/kg cocaine, 40 mg/kg NBQX + 15 mg/kg cocaine, vehicle + 15 mg/kg cocaine, or vehicle + saline daily for 10 days. NBQX did not attenuate activity/stereotypy induced by acute administration of either psychostimulant. Pretreatment with NBQX did not affect augmentation of activity/stereotypy scores by repeated administration of METH or cocaine. There was no significant difference in the intensity of activity/stereotypy between the NBQX + METH and vehicle + METH groups and between the NBQX + cocaine and vehicle + cocaine groups following a challenge injection with 2 mg/kg METH alone or 15 mg/kg cocaine alone, respectively, given 7 days after the last dose of repeated treatment session. Pretreatment with NBQX alone for 10 days (20 mg/kg for 5 days and 40 mg/kg for subsequent 5 days) did not affect the intensity of activity/stereotypy induced by a challenge injection with 2 mg/kg METH given 7 days after the last dose of repeated injection session. NBQX at 40 mg/kg had no apparent effect on acute METH (3 mg/kg)-induced dopamine release in the striatum. These results suggest tht AMPA receptors are unlikely to be involved in induction of behavioral sensitization that is manifested as augmented activity/stereotypy following repeated administration of METH or cocaine.
本研究调查了用α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体拮抗剂2,3-二羟基-6-硝基-7-氨磺酰基苯并[f]喹喔啉（NBQX）进行预处理，对甲基苯丙胺（METH）和可卡因诱导的行为敏化的影响，所用剂量处于相对于诱发急性运动反应以及打断嗅探和头部运动发作的过渡剂量范围。雄性斯普拉格-道利大鼠被随机分为四组，分别每日给予20毫克/千克NBQX + 3毫克/千克METH、40毫克/千克NBQX + 3毫克/千克METH、溶剂 + 3毫克/千克METH或溶剂 + 生理盐水，持续10天。在另一项实验中, 四组大鼠分别每日给予20毫克/千克NBQX + 15毫克/千克可卡因、40毫克/千克NBQX + 15毫克/千克可卡因、溶剂 + 15毫克/千克可卡因或溶剂 + 生理盐水，持续10天。NBQX并未减弱两种精神兴奋剂急性给药所诱发的活动/刻板行为。用NBQX进行预处理并不影响重复给予METH或可卡因后活动/刻板行为评分的增加。在末次重复给药疗程7天后，分别单独给予2毫克/千克METH或15毫克/千克可卡因进行激发注射后，NBQX + METH组与溶剂 + METH组之间以及NBQX + 可卡因组与溶剂 + 可卡因组之间，在活动/刻板行为强度上没有显著差异。单独用NBQX预处理10天（前5天为20毫克/千克，随后5天为40毫克/千克），并不影响在末次重复注射疗程7天后给予2毫克/千克METH激发注射所诱发的活动/刻板行为强度。40毫克/千克的NBQX对急性METH（3毫克/千克）诱导的纹状体多巴胺释放没有明显影响。这些结果表明，AMPA受体不太可能参与行为敏化的诱导过程，行为敏化表现为重复给予METH或可卡因后活动/刻板行为增强。
