健康与遗传心理学研究室知识库

    抑郁症和药物成瘾是当前全球亚待解决的社会问题，两者既相互独立，又有密切的内在联系。虽然抑郁状态可促进复吸的发生，但其对成瘾获得影响的研究较少。为了探讨抑郁状态下吗啡CPP建立的情况，并研究中脑腹侧被盖一伏隔核及黑质一纹状体两条主要的多巴胺神经传导通路所介导的学习机制在其中的作用机制，以及多巴胺D1与D2受体作用的异同，研究首先采用慢性束缚诱发产生抑郁状态，以动物表现出的新颖寻求行为的下降作为抑郁的行为学指标;然后采用一种经典的药物成瘾模型一吗啡条件位置偏爱模型，观察抑郁状态对于吗啡CPP建立的影响;最后采用脑内微量注射的方法，在每次CPP训练前分别选择双侧伏隔核(NAc)和苍白球(globus pallidus)注射D1受体激动剂SKF38393,D2受体激动剂喳毗罗(quinpirole)，探讨多巴胺投射系统在介导抑郁状态影响吗啡CPP建立中的作用。实验结果发现，经过慢性束缚处理后，大鼠表现出一定的抑郁特征，即强迫游泳测试中主动游泳下降及对新颖物体的探究行为减少;抑郁状态能延迟吗啡CPP的建立;苍白球区注射SKF38393, quinpirole，以及伏隔核区注射quinpirole都未能明显改善抑郁状态下吗啡CPP的建立状况，只有在伏隔核区注射SKF38393时明显逆转了抑郁状态对吗啡CPP建立的干扰。实验结果提示，抑郁状态下学习能力的下降可能是抑郁状态干扰吗啡CPP获得的原因，其中相对于黑质一纹状体通路所介导的习惯化学习，中脑腹侧被盖一伏隔核多巴胺投别介导的奖赏相关性学习可能发挥更为重要的作用，尤其是该投射系统中Dl受体系统可能是抑郁状态影响吗啡CPP建立的主要原因。

    Depression and addiction create staggering social problems. They are,  while independent, mutually correlate relapse, however, the influence of depression on establishment of addiction is notd. Depression might be a factor for the addiction clearly understood. The aim of the present studies is to explore this relationship and further to distinguish and analyze the possible role of dopamine D 1 and D2 receptor system, respectively in VTA-NAc and SNc- globus pallidus dopaminergic projections. Main results are listed as follows:
    Experiment 1 found that chronic restraint was an effective method to induce the depressive state. The depressive state was characterized by the behavioral parameter of decrease of novelty seeking behavior in addition to behavioral despair in forced swim test.
    Experiment 2 found that the 1 mg/kg morphine (i.p., three sessions)induced conditioned place preference in control rats, however, the depressive state blocked the acquisition of morphine-induced CPP in the chronic restraint group.
    Experiment 3 found that5 in depressed rats, globus pallidus bilateral microinjection of D1 agonist SKF38393 and D2 agonist quinpirole failed to influence the establishment of CPP, whereas, NAc bilateral microinjection of SKF38393, rather than quinpirole, reversed the effect of depressive state on morphine-induced CPP.
    The above results demonstrated that drug reward was negatively affected by depressive state. Decreased function of dopaminergic projections might be the potential intersection of depression and drug abuse.in which VTA-NAc via D 1 receptor system Impaired reward-related learning played an essential role might be responsible  for  the  blocking  effect  of  depression  on  establishment  of morphine-induced CPP.