Di Chiara G
Department of Toxicology and Consiglio Nazionale delle Ricerche, Center for Neuropharmacology, University of Cagliari, Italy.
J Psychopharmacol. 1998;12(1):54-67. doi: 10.1177/026988119801200108.
The effects of drugs and substances of abuse on central dopamine (DA) transmission studied by in vivo monitoring techniques have been examined and compared with those of conventional reinforcers and in particular with food. The similarities and differences in the action of drugs and conventional reinforcers on DA transmission can provide the basis for an hypothesis of the mechanism of drug addiction and compulsive drug use. This hypothesis states that drug addiction is due to excessive control over behaviour exerted by drug-related stimuli as a result of abnormal motivational learning induced by repeated drug exposure. Such abnormal motivational learning would derive from the repetitive non-habituating property of drugs of abuse to activate DA transmission phasically in the nucleus accumbens (NAc) 'shell'. Thus, activation of DA transmission by conventional reinforcers is under strong inhibitory control by previous exposure to the reinforcer (habituation); this, however, is not the case with drug reinforcers. Repetitive, non-adaptive release of DA in the NAc 'shell' by drugs of abuse would result in abnormal strengthening of stimulus-reward (incentive learning) and stimulus-response associations (habit learning) that constitute the basis for craving and compulsive drug use.
通过体内监测技术研究了药物及滥用物质对中枢多巴胺（DA）传递的影响，并与传统强化物尤其是食物的影响进行了比较。药物和传统强化物对DA传递作用的异同可为药物成瘾及强迫性药物使用机制的假说提供依据。该假说认为，药物成瘾是由于反复接触药物诱导的异常动机学习，导致与药物相关的刺激对行为产生过度控制。这种异常动机学习源于滥用药物在伏隔核（NAc）“壳”中阶段性激活DA传递的重复性、非习惯性特性。因此，传统强化物对DA传递的激活受到先前接触强化物（习惯化）的强烈抑制性控制；然而，药物强化物并非如此。滥用药物在NAc“壳”中重复性、非适应性地释放DA会导致刺激-奖赏（动机学习）和刺激-反应关联（习惯学习）异常增强，而这些关联构成了渴望和强迫性药物使用的基础。
