van der Heyden J A, Bradford L D
Department of Pharmacology, Duphar B.V., Weesp, The Netherlands.
Behav Brain Res. 1988 Nov 1;31(1):61-7. doi: 10.1016/0166-4328(88)90158-1.
Antipsychotics selectively disrupt relatively weak responses maintained by conditioned stimuli compared with stronger responses maintained by unconditioned stimuli. The present study describes an easily taught and rapidly acquired (within one 15-trial session) one-way conditioned avoidance procedure for rats suitable for screening of drugs for potential antipsychotic activity. This was achieved by using an easily acquired response (running, part of the species-specific defense reaction repertoire), a clearly discriminated conditioned stimulus and determination of the appropriate strength of the unconditioned stimulus (i.e. shock level) for this procedure. Behavior acquired under these described conditions resulted in stable performance over long retest periods. By using either a low or high intensity of shock level under which the animals were trained and tested, the difference between the dose of haloperidol and chlorpromazine able to disrupt avoidance and that which disrupted escape response rates was increased. This effect was also observed for morphine, which inhibited both avoidance and escape responses at similar dose levels only under low shock conditions. At a high shock condition morphine more selectively inhibited avoidance responding. Diazepam did not affect avoidance behavior under the conditions described here.
与由非条件刺激维持的较强反应相比，抗精神病药物选择性地破坏由条件刺激维持的相对较弱的反应。本研究描述了一种适用于筛选具有潜在抗精神病活性药物的大鼠单向条件回避程序，该程序易于教授且能在一次15次试验的过程中快速习得。这是通过使用一种易于习得的反应（奔跑，是特定物种防御反应的一部分）、一个能清晰区分的条件刺激以及确定该程序中合适的非条件刺激强度（即电击水平）来实现的。在上述条件下习得的行为在长时间的重新测试期内表现稳定。通过使用动物接受训练和测试时的低强度或高强度电击水平，能够破坏回避反应的氟哌啶醇和氯丙嗪剂量与破坏逃避反应率的剂量之间的差异增大。吗啡也观察到了这种效应，仅在低电击条件下，吗啡在相似剂量水平时抑制回避反应和逃避反应。在高电击条件下，吗啡更具选择性地抑制回避反应。地西泮在此处描述的条件下不影响回避行为。
