Gerhardt S, Liebman J M
Pharmacol Biochem Behav. 1985 Jan;22(1):71-6. doi: 10.1016/0091-3057(85)90488-5.
A variety of anxiogenic substances, benzodiazepine antagonists and antidepressants were tested in a shuttlebox task in which rats interrupted infrared beams to initiate (ON latency) and terminate (OFF latency) continuous rewarding brain stimulation. It was hypothesized that substances exhibiting anxiogenic activity in animals (pentylenetetrazol and beta-CCM) would selectively reduce the OFF latency, since anxiolytic drugs increase this latency. beta-CCM, however, did not alter the OFF latency, but instead lengthened the ON latency. Pentylenetetrazol showed a similar, though not significant, trend. Ro 15-1788 did not alter ON latencies, but selectively lengthened the OFF latency at a high dose, consistent with previously reported anxiolytic activity at such doses. In contrast, CGS 8216 lengthened the ON latency selectively. Thus, Ro 15-1788 was differentiated from other drugs that antagonize benzodiazepines. Caffeine and dopamine uptake-blocking antidepressants (amineptine and nomifensine) preferentially decreased ON latencies, while non-dopamine-blocking antidepressants (viloxazine and CGS 7525A) lengthened both latencies nonspecifically. In conclusion, the OFF latency (but not the ON latency) appears refractory to reduction by various classes of psychotropic agents.
在穿梭箱任务中对多种致焦虑物质、苯二氮䓬拮抗剂和抗抑郁药进行了测试，在该任务中，大鼠打断红外光束以启动（开启潜伏期）和终止（关闭潜伏期）持续的奖励性脑刺激。研究假设，在动物中表现出致焦虑活性的物质（戊四氮和β-CCM）会选择性地缩短关闭潜伏期，因为抗焦虑药物会延长该潜伏期。然而，β-CCM并没有改变关闭潜伏期，反而延长了开启潜伏期。戊四氮也表现出类似的趋势，尽管不显著。Ro 15-1788没有改变开启潜伏期，但在高剂量时选择性地延长了关闭潜伏期，这与之前报道的该剂量下的抗焦虑活性一致。相比之下，CGS 8216选择性地延长了开启潜伏期。因此，Ro 15-1788与其他拮抗苯二氮䓬的药物有所不同。咖啡因和多巴胺摄取阻断型抗抑郁药（阿米替林和诺米芬辛）优先缩短开启潜伏期，而非多巴胺阻断型抗抑郁药（维拉佐嗪和CGS 7525A）则非特异性地延长了两种潜伏期。总之，关闭潜伏期（而非开启潜伏期）似乎对各类精神药物的缩短作用具有抗性。
