健康与遗传心理学研究室知识库

    孕期药物滥用严重危害子代的身心健康，可导致子代学习记忆等认知功能以及成瘾易感性的改变。孕期吸毒可使胎儿脑发育过程发生变化，这种影响可能存在关键期。本实验室前期研究表明，胚胎早期(ES-8 )可能是吗啡影响日龄小鸡学习记忆和成瘾易感性的关键期。为进一步探讨胚胎早期吗啡用药影响日龄小鸡成瘾行为的作用机制，本研究应用离体脑片细胞内记录技术，系统观察了胚胎早期吗啡暴露对日龄小鸡学习记忆和成瘾相关核团一一中间腹内侧原皮质( intermediate medial mesopallium, IMM)突触可塑性及卜氨基丁酸(GABA)能突触传递的影响。结果观察到，胚胎ES-8期接触吗啡的日龄小鸡IMM神经元:1)双脉冲刺激反应比值减小，双脉冲易化诱导率下降;2)异突触长时程增强( long-term potentiation, LTP)诱导率下降，同突触及异突触LTP共存现象缺如，但不影响同突触LTP诱导和维持;3)自发抑制性突触后电位(inhibitory postsynaptic potential, IPSP)的发生率及诱发IPSP的诱导率均下降;4 ) GABAA受体拮抗剂增大去极化突触反应的作用减弱;5)外源性GABAA受体激动剂所诱导的反应幅度降低，GABAB受体激动剂诱导反应的诱导率下降。行为药理学实验表明胚胎早期接触吗啡后的小鸡对吗啡诱导的精神运动兴奋性下降。
    上述结果提示，胚胎早期接触吗啡损害日龄小鸡IMM核团GABA系统功能，并改变了短时程及长时程突触可塑性，该效应可能是胚胎早期吗啡暴露导致子代学习记忆和成瘾行为改变(如学习记忆功能受损，精神运动兴奋性下降等)的重要神经机制之一。

    Drug abuse during pregnancy may result in many serious damages to offspring,including alteration of learning and memory,  cognitive functions and addictive susceptibility. Prenatal opiate exposure may alter developmental process of fetal brain through activation of opioid receptors during the critical period and trigger a range of neuroanatomical and nurobehavioral deficits in offspring. Based on our previous findings in day-old chicks with prenatal morphine-treated, embryonic days 5一8  is crucial for functional development of learning and memory and addiction susceptivity, the  underlying  structure  and  cellular  mechanisms  were  further  explored.  The intermediate medial mesopallium (IMM), a region ofthe chick forebrain, is intimately involved in the early learning processes and addiction, which offers the ideal model to study the neural changes that underlie behavioral plasticity. In current work, the intracellular recordings were conducted from IMM neurons in chick forebrain slices, in  which  electrophysiological  properties,  synaptic  responses  and  long-term potentiation (LTP) were observed. The prenatal morphine-exposed chicks showed attenuation in induction rate of paired-pulse facilitation and heterosynaptic LTP in IMM in vitro. Prenatal morphine exposure during ES一8 also decreased the incidence of spontaneous inhibitory postsynaptic potentials (IPSPs), induction rate of evoked IPSPs, increasing value of evoked EPSPs by bicuculline, amplitude of GABAA responses and induction rate of GABAB responses recorded in IMM neurons from day-old chicks. Morphine-induced psychomotor activity was reduced due to prenatal morphine exposure during ES一8. These results suggest that the altered synaptic plasticity and function of GABAergic system of IMM by early prenatal morphine exposure一is involved in behavioral impairments.