Martin-Iverson M T
Department of Psychology, University of Western Australia, Nedlands, Australia.
J Psychopharmacol. 1999;13(3):261-73. doi: 10.1177/026988119901300320.
There are conflicting reports as to whether or not the effects of dopamine agonist effects at reducing prepulse inhibition of the acoustic startle reflex develop sensitization with repeated treatments. In this experiment, rats (12 per each dose group) were treated for 10 days prior to startle-testing on each day with 0 (vehicle), 50, 200 or 800 microg/kg of apomorphine. Startle testing was conducted with each rat receiving no stimulus trials (null trials), startle pulse only trials (40 ms 105 dB white noise), prepulse only trials (20 ms 72 dB 5 kHz tone) and prepulse+pulse trials with a 100 ms stimulus onset asynchrony (SOA, i.e. the lead time from onset of prepulse to onset of pulse). The rats were then challenged after 5-7 days of withdrawal from the treatment regimen with a vehicle and apomorphine (200 microg/kg) injection with the order of injection counterbalanced. A range of SOAs and two different prepulse intensities (68 and 70 dB) were presented to every rat on the challenge tests. Sensitization developed during treatment to the increase in motor activity produced by the two higher doses, and to the increase in an orienting response produced by the prepulse stimulus in the highest dose group, but not to the prepulse inhibition effect of the drugs. The 50 microg/kg inhibitory autoreceptor selective dose decreased responses on the first of three blocks of both null trials and prepulse only trials. The two higher doses dose-dependently increased startle reflex amplitudes on the prepulse+pulse trials (reduced prepulse inhibition), but this effect did not exhibit sensitization during treatment. The lowest dose significantly increased prepulse inhibition relative to the vehicle-treated group on the first block of trials over days. After apomorphine challenge, sensitization to the effects of apomorphine on reducing prepulse inhibition was apparent for some dose groups at some SOAs. Sensitization to the effects of apomorphine on prepulse inhibition can be demonstrated upon a subsequent drug challenge if pretreatments are associated exclusively with the startle testing environment.
关于多巴胺激动剂降低听觉惊吓反射的前脉冲抑制作用在重复给药后是否会产生敏化，存在相互矛盾的报道。在本实验中，大鼠（每个剂量组12只）在每天进行惊吓测试前10天，分别用0（溶剂）、50、200或800微克/千克的阿扑吗啡进行处理。对每只大鼠进行惊吓测试时，分别进行无刺激试验（空白试验）、仅惊吓脉冲试验（40毫秒105分贝白噪声）、仅前脉冲试验（20毫秒72分贝5千赫纯音）以及前脉冲+脉冲试验，刺激起始异步时间（SOA，即从前脉冲起始到脉冲起始的提前时间）为100毫秒。然后，在停止给药方案5 - 7天后，对大鼠进行溶剂和阿扑吗啡（200微克/千克）注射激发试验，注射顺序相互平衡。在激发试验中，对每只大鼠呈现一系列的SOA以及两种不同的前脉冲强度（68和70分贝）。在治疗期间，对两个较高剂量所产生的运动活动增加以及最高剂量组中前脉冲刺激所产生的定向反应增加产生了敏化，但对药物的前脉冲抑制作用未产生敏化。50微克/千克的抑制性自身受体选择性剂量在空白试验和仅前脉冲试验的三个试验组中的第一个试验组中降低了反应。两个较高剂量在前脉冲+脉冲试验中剂量依赖性地增加了惊吓反射幅度（降低了前脉冲抑制），但这种作用在治疗期间未表现出敏化。在试验的第一天，最低剂量相对于溶剂处理组显著增加了前脉冲抑制。在阿扑吗啡激发试验后，对于某些剂量组在某些SOA下，对阿扑吗啡降低前脉冲抑制作用的敏化是明显的。如果预处理仅与惊吓测试环境相关，则在随后的药物激发试验中可以证明对阿扑吗啡前脉冲抑制作用的敏化。
