摘要
目的研究M胆碱能受体阻滞剂东莨菪碱对猕猴吗啡静脉自身给药及反应恢复行为的影响。方法建立猕猴吗啡静脉自身给药模型(固定比率1 ,给药期4h)以及反应恢复模型。观察不同浓度东莨菪碱急性处理对吗啡静脉自身给药模式、踏板反应率、吗啡用药量以及自由活动度的影响。同时观察慢性和急性东莨菪碱处理对静脉自身给药行为淬灭后反应恢复行为的影响。结果东莨菪碱急性处理(0.025,0.075,0.25,0.75mg/kg)可以减弱FR1程序控制下吗啡静脉自身给药行为 ,不仅表现为总用药量和反应速率的降低 ,而且还可延迟自身给药行为的起动 ,同时对自身给药行为模式有较大的影响 ,小剂量东莨菪碱可使急促的用药行为变为缓慢 ,大剂量时几乎可完全阻断动物的踏板反应。反应恢复实验结果显示 ,东莨菪碱急性处理可延迟淬灭后踏板反应的恢复 ,而慢性处理可降低动物的踏板反应率及总的强化次数。
Aim To study the effects of scoplamine, a marscarinic receptor antagonist on intravenous morphine self_administration and reinstatement of responding in rhesus monkeys (fixed ratio 1, FR1).Methods Rhesus monkeys were trained to press response lever for intravenous morphine self_administration under a fixed ratio 1 schedule in a daily 4 h session. Response pattern, total response rate, total mophine intake and spontaneous activity were recorded during sessions. Effects of acute pretreatment with different doses of scopolamine on self_administration were studied, and also the effects of acute and chronic treatment with scopolamine on reinstatement of responding by priming dose of morphine were observed after extinction of self_administration were observed. Results The results showed that acute treatment of scopolamine (0.025～0.75 mg/kg) could not only attenuate intravenous morphine self_administration under a FR1 schedule, which was represented by decreased total morphine intake and response rate per session, but also delay the initiation of morphine self_administration.The response pattern was affected under this treatment. Chroniceffect of scoplamine was also evaluated after extinction during which a daily dose of scopolamine(0.25 mg/kg) was administered,and in the testing day,only a priming dose of morphine (0.25 mg/kg) was administered. Chronic scopolamine treatment caused 45% decrease of response rate by morphine priming. Conclusion Chronic scopolamine treatment might inhibit the reinstatement of responding after extinction.
