石杉碱甲对应激诱导的吗啡行为敏感化表达的影响

Effects of Huperzine A on Stress Induced Expression of Morphine Behavioral Sensitization

为探讨石杉碱甲对应激诱导的吗啡行为敏感化表达的影响,将40只动物随机分为5组:盐水组、石杉碱甲组、吗啡组、应激组、石杉碱甲+应激组。实验发现,急性/慢性空瓶应激都能够激发吗啡行为敏感化的表达,而石杉碱甲能够显著抑制空瓶应激的这种激发作用。经过吗啡点燃后,急性空瓶应激并不能显著影响动物的行为敏感化,提示与成瘾性药物的再现相比,空瓶应激对动物的影响力度较小。研究结果表明,石杉碱甲能够抑制急性/慢性空瓶应激诱导的吗啡行为敏感化表达,表明这类胆碱酯酶抑制剂有可能成为治疗药物依赖的潜在药物。

Behavioral sensitization is defined as an increased behavioral response after repeated intermittent treatment with various drugs of abuse and is thought to be involved in drug abuse and addiction. This experiment examined the effects of Huperzine A on stress-induced expression of morphine behavioral sensitization in rats. Rats were treated with saline or morphine （3 mg/kg） for 7 days to induce behavioral sensitization （defined as a progressive increase of locomotor activity in the current study）. In the subsequent experimental sessions, a stressor （empty bottle during scheduled water availability） was introduced acutely or chronically to elicit expression of morphine sensitization. The locomotor activities of the rats were monitored daily by using computer-interfaced monitoring system. The distance traveled （cm） during the development period was analyzed by two-way ANOVA with treatment day as the repeated measure. The data from the two challenge tests were separately analyzed by one-way ANOVA. Post hoc analyses （LSD test） were performed for assessing specific group comparison. Morphine induced significant behavioral sensitization during daily treatment. Environmental cue elicited marked hyperactivity during morphine discontinuation, which gradually dissipated within 7 days. Acute or chronic stress treatment both markedly induced expression of behavioral sensitization. A challenge dose of morphine markedly elicited the expression of behavioral sensitization, which was prevented by Huperzine A. In conclusion, this study demonstrated that stress induces robust expression of morphine sensitization and this can be inhibited by a cholinesterase inhibitor Huperzine A. This suggests that drugs that act as cholinesterase inhibitors （e.g. Huperzine A） may be useful therapeutics for opioid addiction.