Kornetsky C, Esposito R U, McLean S, Jacobson J O
Arch Gen Psychiatry. 1979 Mar;36(3):289-92. doi: 10.1001/archpsyc.1979.01780030055004.
We present the thesis that many drugs of abuse are used for their hedonic effects and that a relevant animal model for the study of these effects is the action of these drugs on the pathways that support rewarding intracranial self-stimulation. A relationship between abuse potential of a drug and its ability to lower the threshold for rewarding brain stimulation in the rat was found. Of all the compounds we have studied, morphine and cocaine were the drugs that caused the maximum lowering of the rewarding threshold. Phencyclidine hydrochloride and the mixed agonist-antagonist pentazocine also lowered the threshold to a lesser degree, while the mixed agonist-antagonists cyclazocine and nalorphine hydrochloride had inconsistent effects. Naloxone hydrochloride, at the doses tested, had no effect on the threshold. Further, there is no evidence that tolerance develops to the threshold-lowering effect of morphine, suggesting that continued use of narcotics by the physically dependent individual is not simply due to an effort to avoid the pain of withdrawal.
许多滥用药物是因其享乐效应而被使用，并且研究这些效应的一个相关动物模型是这些药物对支持颅内自我刺激奖赏的通路的作用。发现一种药物的滥用潜力与其降低大鼠脑刺激奖赏阈值的能力之间存在关联。在我们研究的所有化合物中，吗啡和可卡因是导致奖赏阈值降低最多的药物。盐酸苯环己哌啶和混合激动剂 - 拮抗剂喷他佐辛也在较小程度上降低了阈值，而混合激动剂 - 拮抗剂环唑辛和盐酸纳洛芬的作用则不一致。在所测试的剂量下，盐酸纳洛酮对阈值没有影响。此外，没有证据表明对吗啡的阈值降低效应会产生耐受性，这表明身体依赖个体持续使用麻醉品不仅仅是为了避免戒断痛苦。
