Tramullas Mónica, Martínez-Cué Carmen, Hurlé María A
Departamento de Fisiología y Farmacología, Universidad de Cantabria, Santander, Spain.
Behav Brain Res. 2008 Jun 3;189(2):332-40. doi: 10.1016/j.bbr.2008.01.013. Epub 2008 Feb 5.
Although the repercussion of chronic treatment with large amounts of opioids on cognitive performance is a matter of concern, the effects of opioid drugs on passive avoidance learning have been scarcely studied. Here, we analyzed the effects of prolonged administration of heroin and methadone, as well as the impact of suffering repeated episodes of withdrawal on fear-motivated learning using the passive avoidance test. Mice received chronic treatment (39 days) with methadone (10 mg/kg/24 h), associated or not with repeated withdrawal episodes, or with heroin (5 mg/kg/12 h). Our results show that, regardless of the type of treatment received, all mice displayed similar basal thermal nociceptive thresholds during 25 days of treatment. In the hot plate test, both methadone and heroin induced antinociception 30 min after drug administration. The analgesic effect was absent when measured 4 h after heroin and 12 h after methadone. Pain behavioural responses elicited by growing intensities of electric shock, applied on day 28th of treatment, were similar in all groups of mice. Our results indicate that chronic opioid treatment had promnesic effects on passive avoidance behaviour in mice, unrelated to changes in the nociceptive state.
尽管长期大量使用阿片类药物对认知能力的影响令人担忧，但阿片类药物对被动回避学习的影响却鲜有研究。在此，我们使用被动回避试验分析了海洛因和美沙酮长期给药的影响，以及反复戒断发作对恐惧动机学习的影响。小鼠接受了美沙酮（10毫克/千克/24小时）的长期治疗（39天），无论是否伴有反复戒断发作，或接受海洛因（5毫克/千克/12小时）治疗。我们的结果表明，无论接受何种治疗，所有小鼠在25天的治疗期间均表现出相似的基础热痛觉阈值。在热板试验中，美沙酮和海洛因在给药后30分钟均诱导了抗伤害感受作用。在海洛因给药4小时后和美沙酮给药12小时后测量时，镇痛效果消失。在治疗第28天施加强度不断增加的电击所引发的疼痛行为反应，在所有小鼠组中均相似。我们的结果表明，慢性阿片类药物治疗对小鼠的被动回避行为具有记忆增强作用，与伤害感受状态的变化无关。
