健康与遗传心理学研究室知识库

成瘾发生主要与急性的奖赏效应以及反复作用后中脑边远多巴胺系统的长时程适应性变化有关。自然奖赏物同样激活该系统产生奖赏效应，寻求和获取自然奖赏物的行为也受到该系统调控。为了探讨自然奖赏和药物奖赏之间的相互关系，并研究成瘾药物反复作用导致的神经变化对自然奖赏行为的影响及其机制。研究首先通过测量大鼠对新颖奖赏的反应和药物奖赏效应来研究两种奖赏的关系;然后采用蔗糖水为自然奖赏物，研究吗啡反复给药后蔗糖水饮用行为的变化，以及DA机制，最后使用双侧NAC微注射DA丁阻断剂和p受体激动剂的方法，深入研究该机制。发现大鼠新颖寻求行为的高低能够预测吗啡诱导CPP的高低，而且慢性吗啡处理能够增加大鼠的新颖寻求行为。腹腔注射DA丁阻断剂能特异性增加蔗糖水饮用行为:反复吗啡处理将这种效应加强，产生敏感化，但是不影响自然条件下的蔗糖水饮用行为。NAC微注射DAT阻断剂能够特异性增加蔗糖水饮用行为，但是没能发现反复吗啡处理的影响。结果提示药物奖赏和自然奖赏之间可能有共同的DA神经基础，表明反复药物处理后，自然奖赏行为在获取动机方面有敏感化现象且有MLDS的参与;这种动机敏感化也可能是导致成瘾的主要原因。

It is widely accepted that Addiction is induced by the direct reward effect of addictive drug and by the long-term change of rnesolimbic dopaminergic system (MLDS) after drug exposure. The natural rewards activate the MLDS similarly by increasing extracellular dopamine levels in the nucleus accumbens (NAC) following acute administration, and the approach and appetite behavior to nature reward is also mediated by MLDS. The aim of present studies is to determine the interaction of natural reward and drug reward, the effects of repeated drug treatment on natural reward and the neural mechanism.
Experiment 1 found that pretreatment with morphine enhanced the response to novelty object of rats. And naive rats that with high response to novelty produced higher conditional place preference induced by morphine than that of low responders.
Experiment 2 found that chronic morphine pretreatment did not make the licking behavior sensitive to sucrose solution, but sensitized the augmentation effect of sucrose intake by the dopamine uptake blockade nomifensine. Moreover, the enhance effect of nomifensine was reversed by D1 receptor antagonist SCH 23390.
Experiment 3 found that sucrose consumption was specifically increased by NAC bilateral microinjection of DAT inhibiter GBR 12909, but not by preceptor agonist morphine. In the same time, it was not found the effect of chromic morphine pretreatment in this experiment.
These studies proved that drug reward and non-drug reward had same neural mechanism. Repeatted exposure to reward could sensitize not only the effect of addictive drug but also the nature reward seeking behavior.