健康与遗传心理学研究室知识库

    多种学习一记忆系统参与成瘾行为的形成，其中联想性学习发挥着重要的作用。研究围绕吗啡的精神运动兴奋性和奖赏两个最基本的作用，考察联想性学习是否参与吗啡诱导小鸡条件性运动和条件性奖赏及其神经机制。虽然成瘾研究中常用哺就动物，但因为小鸡在学习一记忆机制研究中的优点，因此，它可以作为建立成瘾行为模型一种合适的实验动物。研究采用自发活动量( locomoter  activity,  LA) ）GI条件性位置偏爱( conditioned  place preference, CPP)的成瘾动物模型和脑内微量注射相结合的方法。首先考察了吗叫卜的精神运动兴奋性和奖赏作用在小鸡中的体现。发现小剂量吗啡能显著增加小鸡的LA，吗啡诱导产生了小鸡行为敏感化;验证了吗啡诱导也可以产生小鸡的CPP。研究还发现多巴胺(dopami.ne,  DA)系统在吗啡诱导小鸡产生成瘾行为中的作用，多巴)fJ转运子拮抗剂诺米芬新显著的增加了吗啡处理组小鸡的自发活动量，多巴胺D1受体拮抗剂SCH23390而不是D2受体拮抗剂雷氯必利能阻断吗啡诱导小鸡CPP的表达。最后使用脑内微量注射的方法，深入研究联想性学习参与条件化运动和条件化奖赏的神经机制。发现双侧LPO微量注射多巴胺D1受体拮抗剂SCH23390和NMDA受体拮抗剂MK-801以及双侧工MHV微量注射MK-801都阻断了吗啡诱导的C即和条件性化运动的形成。双侧LPO微量注射多巴胺D2受体拮抗剂螺呱隆阻断了吗啡诱导的条件化运动的形成。工MHV微量注射SCH23390阻断了吗啡诱导的小鸡C即的形成。结果提示，吗啡的奖赏效应和精神运动兴奋性效应在小鸡中也能体现，小鸡可以作为研究成瘾行为的适合的实验动物。LPO的Dl和谷氨酸受体、工MHV的谷氨酸受体同时参与两种联想性学习，LPO的D2受体参与运动的联想性学习，而工MFIV的D1受体参与奖赏的联想性学习。参与环境和吗啡奖赏作用的联想性学习和参与环境和吗啡精神运动兴奋性的联想性学习之间的神经生物学基础不尽相同。

    Several learning  and memory  systems  are  involved  in  the development of  addictive behavior, in which associative learning pays an important role. Though mammals are always used to study the mechanism of  addictive behavior, the chick may be an appropriate model for its advantage in the research of learning and memory. The aims of present studies are to develop the behavioral models induced by morphine in chicks and determine the neural mechanism of associative learning underlying  addictive behavior，such as conditioned activity and conditioned reward, by using   the combination of animal models of addiction., such as locomotor activity and conditioned place preference, and the microinjection technique.
    Experiment 1 showed that repeated administration of low dose of morphine  significantly  elicited  progressive locomotor activity relative to saline. The  locomotor responses to the dopamine reuptake Mocker nomifensine were also dose-dependently sensitized in chicks pre一exposed with morphine.
    Experiment 2 indicated that morphine produced conditioned place preference on chicks. The injection of SCH23390 but not raclopride abolished the expression of morphine-induced CPP.
    Experiment 3 showed that LPO bilateral microinjection of SCH23390  and  NMDA  receptor inhibiter MK-801 or IMHV bilateral microinjection of MK-801 all abolished the development of morphine-induced CPP and conditioned activity. LPO bilateral microinjection of while spiperone abolished conditioned behavioral sensitization.IMHV bilateral  microinjection of SCH23390 abolished  morphine-induced CPP.
    These studies  suggested  that the rewarding and psychomotor stimulant  effects of  morphine  might  be  highly  conserved  across species. Chick might  serve as an lternative  animal  model  for investigating addictive behavior. The mechanism of the associative learning between the rewarding and psychomotor effects of morphine was not all the same.