Knapp C M, Kornetsky C
Laboratory of Behavioral Pharmacology, Boston University School of Medicine, MA 02118.
Pharmacol Biochem Behav. 1989 Apr;32(4):977-82. doi: 10.1016/0091-3057(89)90069-5.
Thresholds for rewarding brain stimulation delivered to the medial forebrain bundle-lateral hypothalamus were determined by means of a rate-free psychophysical method. Amfonelic acid (AFA), an indirect dopamine agonist, alone caused a significant dose-dependent lowering of the rewarding threshold. Although naloxone treatment by itself did not significantly alter the reward threshold, it blocked AFA's threshold lowering effect in every animal at one or more of the dose combinations of the two drugs tested. Naloxone was found to be more effective in blocking the threshold lowering actions of a higher (1 mg/kg) dose as opposed to a lower (0.25 mg/kg) dose of AFA. Since a lowering of threshold for rewarding intracranial stimulation is a model for drug-induced euphoria, the findings presented here indicate that AFA may have abuse potential. Furthermore, these results suggest that endogenous opioid systems may begin to modulate the effects of AFA on the reward system only when a certain level of activation of dopaminergic systems is reached.
通过一种无速率的心理物理学方法确定了给予内侧前脑束-外侧下丘脑的脑刺激奖励阈值。安非他明酸（AFA），一种间接多巴胺激动剂，单独使用时会导致奖励阈值显著的剂量依赖性降低。虽然单独使用纳洛酮治疗并没有显著改变奖励阈值，但在测试的两种药物的一个或多个剂量组合下，它在每只动物中都阻断了AFA的阈值降低作用。发现纳洛酮在阻断较高剂量（1mg/kg）而非较低剂量（0.25mg/kg）的AFA的阈值降低作用方面更有效。由于颅内刺激奖励阈值的降低是药物诱导欣快感的一种模型，此处呈现的研究结果表明AFA可能具有滥用潜力。此外，这些结果表明，只有当多巴胺能系统达到一定程度的激活时，内源性阿片系统才可能开始调节AFA对奖励系统的作用。
