Wang Zhixia, Woolverton William L
Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, 2500 N. State Street, Jackson, MS 39216, USA.
Pharmacol Biochem Behav. 2009 Feb;91(4):590-5. doi: 10.1016/j.pbb.2008.09.013. Epub 2008 Oct 7.
Histamine H1 receptor antagonists can be sedating and have behavioral effects, including reinforcing and discriminative stimulus effects in non-humans, that predict abuse liability. Previous research has suggested that antihistamines can enhance the effects of some drugs of abuse. We have reported a synergistic interaction between cocaine and diphenhydramine (DPH) in a self-administration assay with monkeys. The present study was designed to extend those findings to other combinations of cocaine and DPH, and to the mixture of cocaine and another H1-antihistamine, pyrilamine. Rhesus monkeys were prepared with chronic i.v. catheters and allowed to self-administer cocaine, DPH or pyrilamine alone or as mixtures under a progressive-ratio schedule of reinforcement. Cocaine, DPH and pyrilamine alone maintained self-administration and cocaine was the stronger reinforcer. When cocaine was combined with DPH or pyrilamine in a 1:1, 1:2 or 2:1 ratio of the ED(50)s, the combinations were super-additive as reinforcers. Reinforcing strength of the combinations was greater than that of the antihistamines alone but not greater than cocaine. The data support the prediction that the combination of cocaine and histamine H1 receptor antagonists could have enhanced potential for abuse relative to either drug alone. The interaction may involve dopamine systems in the CNS.
组胺H1受体拮抗剂具有镇静作用并能产生行为效应，包括在非人类动物中具有强化和辨别刺激效应，这些效应预示着药物滥用的可能性。先前的研究表明，抗组胺药可增强某些滥用药物的作用。我们曾报道在猴子的自我给药试验中，可卡因与苯海拉明（DPH）之间存在协同相互作用。本研究旨在将这些发现扩展至可卡因与DPH的其他组合，以及可卡因与另一种H1抗组胺药吡苄明的混合物。给恒河猴植入慢性静脉导管，使其在渐进比率强化程序下单独或混合自我给药可卡因、DPH或吡苄明。单独使用时，可卡因、DPH和吡苄明均可维持自我给药行为，且可卡因是更强的强化剂。当可卡因与DPH或吡苄明按ED(50)的1:1、1:2或2:1比例混合时，这些组合作为强化剂具有超相加性。组合的强化强度大于单独使用抗组胺药，但不大于可卡因。这些数据支持如下预测：相对于单独使用任何一种药物，可卡因与组胺H1受体拮抗剂的组合可能具有更高的滥用潜力。这种相互作用可能涉及中枢神经系统中的多巴胺系统。
