Izenwasser S, Kornetsky C
Laboratory of Behavioral Pharmacology, Boston University School of Medicine, MA 02118.
Pharmacol Biochem Behav. 1989 Apr;32(4):983-6. doi: 10.1016/0091-3057(89)90070-1.
Many drugs of abuse, including stimulants such as cocaine and amphetamine, and opioids like morphine and heroin, will lower threshold at which rats will work to receive electrical stimulation to the medial forebrain bundle-lateral hypothalamic region (MFB-LH). This effect is even greater when the two classes of drugs are coadministered. The underlying mechanisms by which this occurs are not completely understood, however there is considerable evidence suggesting that the catecholamines play a major role in mediating the reinforcing effects of these drugs. The present study was conducted to investigate the effects of amfonelic acid, an indirect dopamine agonist, and nisoxetine, a highly selective norepinephrine uptake blocker, alone and in combination with morphine, on the reward threshold for rewarding electrical intracranial stimulation. As in previous studies, morphine, as well as amfonelic acid, lowered the reward threshold with the amfonelic acid causing greater threshold lowerings than that of morphine. When a low (ineffective) dose of amfonelic acid was administered concomitantly with morphine, the threshold lowerings observed were larger than those seen with either drug alone and were often more than additive. Nisoxetine alone had no effect on the reward threshold and produced inconsistent results when combined with morphine. These findings support the thesis that amfonelic acid has abuse potential, and that its reinforcing effects may, in fact, be even greater than that of the opioids. Further, these results support the hypothesis that dopamine plays a more critical role in mediating brain-stimulation reward than dose norepinephrine.
许多滥用药物，包括可卡因和苯丙胺等兴奋剂，以及吗啡和海洛因等阿片类药物，都会降低大鼠为接受内侧前脑束-外侧下丘脑区域（MFB-LH）的电刺激而工作的阈值。当这两类药物联合使用时，这种效果会更明显。虽然这种现象发生的潜在机制尚未完全明确，但有大量证据表明，儿茶酚胺在介导这些药物的强化作用中起主要作用。本研究旨在探究间接多巴胺激动剂安福芬酸和高选择性去甲肾上腺素摄取阻滞剂尼索西汀单独使用以及与吗啡联合使用时，对颅内电刺激奖赏阈值的影响。与之前的研究一样，吗啡以及安福芬酸都降低了奖赏阈值，且安福芬酸导致的阈值降低幅度比吗啡更大。当低剂量（无效）的安福芬酸与吗啡同时给药时，观察到的阈值降低幅度比单独使用任何一种药物时都大，且往往超过相加效应。单独使用尼索西汀对奖赏阈值没有影响，与吗啡联合使用时结果不一致。这些发现支持了安福芬酸具有滥用潜力这一论点，而且其强化作用实际上可能比阿片类药物更强。此外，这些结果支持了多巴胺在介导脑刺激奖赏方面比去甲肾上腺素起更关键作用这一假说。
