van Ree J M, Burbach-Bloemarts E M, Wallace M
Rudolf Magnus Institute for Pharmacology, Medical Faculty, University of Utrecht, The Netherlands.
Life Sci. 1988;42(10):1091-9. doi: 10.1016/0024-3205(88)90565-6.
The effect of the vasopressin neuropeptide des-glycinamide (Arg8)-vasopressin (DGAVP) on reducing the acquisition of intravenous heroin self-administration in rats was analyzed. When rats reduced in body weight were allowed to self-administer heroin for 1 h per day in the presence of a fixed time, non contingent food delivery schedule, it appeared that heroin intake was related in an orderly way to the unit dose of heroin delivered. DGAVP decreased heroin intake during days 4 and 5 of acquisition, especially when a high dose of heroin was delivered. DGAVP decreased heroin intake more effectively when rats were tested without the food delivery schedule and for 6 h instead of 1 h sessions per day. Structure activity relationship studies revealed that the peptide (pGlu4, Cyt6)AVP-(4-8) was the shortest active sequence mimicking the effect of DGAVP and that this peptide was somewhat more potent than DGAVP in this respect. The peptide (pGlu4,Cyt6)AVP-(4-9) increased the heroin intake of the rats. DGAVP and (pGlu4,Cyt6)-AVP-(4-8) also decreased cocaine intake of body weight reduced rats given the opportunity to self-administer cocaine intravenously in daily 6 h sessions. It is concluded that vasopressin neuropeptides may decrease the reinforcing efficacy of heroin and cocaine during acquisition of drug self-administration rather than interact with nutritional and environmental factors influencing drug taking behavior.
分析了血管加压素神经肽去甘氨酰胺（精氨酸8）-血管加压素（DGAVP）对减少大鼠静脉注射海洛因自我给药习得的影响。当体重减轻的大鼠在固定时间、非偶然食物投放时间表的情况下，每天被允许自我给药海洛因1小时时，海洛因摄入量似乎与投放的海洛因单位剂量呈有序相关。DGAVP在习得的第4天和第5天减少了海洛因摄入量，尤其是当投放高剂量海洛因时。当大鼠在没有食物投放时间表的情况下进行测试，且每天测试6小时而非1小时时，DGAVP能更有效地减少海洛因摄入量。构效关系研究表明，肽（焦谷氨酸4，胞嘧啶6）血管加压素-（4-8）是模拟DGAVP作用的最短活性序列，并且在这方面该肽比DGAVP稍强。肽（焦谷氨酸4，胞嘧啶6）血管加压素-（4-9）增加了大鼠的海洛因摄入量。DGAVP和（焦谷氨酸4，胞嘧啶6）-血管加压素-（4-8）也减少了有机会每天6小时静脉自我给药可卡因的体重减轻大鼠的可卡因摄入量。得出的结论是，血管加压素神经肽可能在药物自我给药习得过程中降低海洛因和可卡因的强化效力，而不是与影响药物摄取行为的营养和环境因素相互作用。
