Jackson D M, Bengtsson A, Johansson C, Cortizo L, Ross S B
Department of Behavioural, Preclinical CNS Research and Development, Södertälje, Sweden.
Neuropharmacology. 1994 Aug;33(8):1003-9. doi: 10.1016/0028-3908(94)90159-7.
We examined the effects of manipulating 5-HT1A receptors on the performance of a passive avoidance task in rats. Firstly, we studied the effect of racemic 8-OH-DPAT and compared it to the pure enantiomers (subcutaneous injection, s.c.). Secondly, we investigated the effect (s.c.) of the selective 5-HT1A receptor antagonist (S)-UH-301 [(S)-5-fluoro-8-hydroxy-2-(dipropylamino)tetralin] both alone and on 8-OH-DPAT-induced disruption of acquisition. Thirdly, we examined whether tolerance occurs to the effects of 8-OH-DPAT on passive avoidance acquisition. Finally, we examined the effects (s.c.) of the selective NMDA receptor antagonist dizocilpine, (+)-MK-801[(5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohe pten-5, 10-imine], on this tolerance development. Different doses of racemic 8-OH-DPAT were injected 10 min before rats were exposed to the acquisition phase of a step through passive avoidance response. When tested for retention 24 h later, 8-OH-DPAT-pretreated rats failed to exhibit any avoidance. R(+) and S(-)-8-OH-DPAT were also active with the R(+)-isomer being more active than the S(-)-isomer. The 5-HT1A antagonist (S)-UH-301 [(S)-5-fluoro-8-hydroxy-2-(dipropylamino)tetralin] was without effect on avoidance performance but antagonized the effect of 8-OH-DPAT. In a further experiment, rats were pretreated with racemic 8-OH-DPAT (0.3 mg/kg). Twenty four hours later, they received a challenge dose of 8-OH-DPAT and exposed to the acquisition phase of the avoidance response. When tested 24 hr later for retention, 8-OH-DPAT challenged rats failed to show any indication of an avoidance response.(ABSTRACT TRUNCATED AT 250 WORDS)
我们研究了操控5-羟色胺1A（5-HT1A）受体对大鼠被动回避任务表现的影响。首先，我们研究了消旋8-羟基二丙胺四氢萘（8-OH-DPAT）的作用，并将其与纯对映体（皮下注射）进行比较。其次，我们研究了选择性5-HT1A受体拮抗剂（S）-UH-301 [（S）-5-氟-8-羟基-2-（二丙基氨基）四氢萘]单独使用时以及对8-OH-DPAT诱导的习得破坏的影响（皮下注射）。第三，我们研究了8-OH-DPAT对被动回避习得的影响是否会产生耐受性。最后，我们研究了选择性N-甲基-D-天冬氨酸（NMDA）受体拮抗剂地佐环平，（+）-MK-801 [（5R，10S）-（+）-5-甲基-10，11-二氢-5H-二苯并（a，d）环庚烯-5，10-亚胺]对这种耐受性发展的影响（皮下注射）。在大鼠进入一步通过式被动回避反应的习得阶段前10分钟，注射不同剂量的消旋8-OH-DPAT。在24小时后进行记忆测试时，经8-OH-DPAT预处理的大鼠未表现出任何回避行为。R（+）和S（-）-8-OH-DPAT也有活性，R（+）异构体比S（-）异构体更具活性。5-HT1A拮抗剂（S）-UH-301 [（S）-5-氟-8-羟基-2-（二丙基氨基）四氢萘]对回避表现没有影响，但拮抗了8-OH-DPAT的作用。在进一步的实验中，用消旋8-OH-DPAT（0.3毫克/千克）对大鼠进行预处理。24小时后，它们接受一次8-OH-DPAT的激发剂量，并进入回避反应的习得阶段。在24小时后进行记忆测试时，经8-OH-DPAT激发的大鼠未表现出任何回避反应的迹象。（摘要截选至250字）
