Treit D
Pharmacol Biochem Behav. 1985 Jan;22(1):47-52. doi: 10.1016/0091-3057(85)90484-8.
The hypothesis that analgesic mechanisms might account for the suppressive effect of diazepam on defensive burying was tested in four experiments. In the first experiment, 1 mg/kg of diazepam had no appreciable effect on rat's latency to escape from a painful heat stimulus, but reliably suppressed defensive burying behavior. There was no significant relationship between the diazepam-treated rats' latency to escape and their duration of burying. Rats in Experiment 2 were injected with diazepam during a delay between shock and testing, so that they could not be experiencing the putative analgesic effect of diazepam during the shock. In spite of this, diazepam produced a significant suppression of burying compared to saline control. In the next experiment, the effect of diazepam on defensive burying was assessed in the complete absence of painful stimulation by exposing the rats to a novel stimulus known to elicit burying behavior. Diazepam suppressed burying behavior to the novel stimulus in a dose-dependent fashion. Finally, the ability of 10 mg/kg of naloxone to reverse the suppressive effect of 1 mg/kg of diazepam was assessed in Experiment 4. Naloxone failed to reverse the suppressive effect of diazepam and had no significant effect on defensive burying by itself, suggesting that the modulating influence of diazepam on rats' defensive burying behavior did not depend upon endogenous opiate mechanisms. Taken together, the results of the four experiments did not support the view that benzodiazepines produce their anxiolytic effects through analgesic mechanisms.
在四项实验中对镇痛机制可能解释地西泮对防御性埋土行为的抑制作用这一假设进行了测试。在第一项实验中,1毫克/千克的地西泮对大鼠从疼痛热刺激中逃脱的潜伏期没有明显影响,但可靠地抑制了防御性埋土行为。接受地西泮治疗的大鼠的逃脱潜伏期与其埋土持续时间之间没有显著关系。实验2中的大鼠在电击和测试之间的延迟期间注射了地西泮,因此它们在电击期间不会体验到地西泮假定的镇痛作用。尽管如此,与生理盐水对照组相比,地西泮对埋土行为仍有显著抑制作用。在下一项实验中,通过将大鼠暴露于已知能引发埋土行为的新刺激下,在完全没有疼痛刺激的情况下评估了地西泮对防御性埋土行为的影响。地西泮以剂量依赖的方式抑制了对新刺激的埋土行为。最后,在实验4中评估了10毫克/千克纳洛酮逆转1毫克/千克地西泮抑制作用的能力。纳洛酮未能逆转地西泮的抑制作用,并且其本身对防御性埋土行为没有显著影响,这表明地西泮对大鼠防御性埋土行为的调节作用并不依赖于内源性阿片机制。综上所述,这四项实验的结果不支持苯二氮䓬类药物通过镇痛机制产生抗焦虑作用的观点。