Martin T J, Smith J E, Dworkin S I
Center for the Neurobiological Investigation of Drug Abuse, Department of Physiology and Pharmacology, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC 27157-1083, USA.
Pharmacol Biochem Behav. 1998 Jun;60(2):415-21. doi: 10.1016/s0091-3057(97)00599-6.
In this study a rat self-administration model was used to examine the effects of training dose and time in the session on the dose-effect curve for heroin. Doses of heroin lower than 5.4 microg/inf maintained higher rates of drug intake in animals trained with 5.4 microg/inf compared to 18 microg/inf. Doses greater than 5.4 microg/inf maintained similar rates of intake in both groups of animals. The dose-response curve was shifted downward and to the right as the session progressed for animals trained with 5.4 microg/inf of heroin; however, the shift in the dose-intake curve over the session was less pronounced when the training dose was 18 microg/inf. Naltrexone and naltrindole were administered to animals in which responding was engendered with infusions of 5.4 microg of heroin to determine the effects of these antagonists in the context of time is the session. The potency of naltrexone decreased across the 4 h of the session with a time course that was consistent with literature reports on the elimination kinetics of naltrexone in rat brain. In contrast, there was not a significant interaction between naltrindole dose and session time. Therefore, the rates of heroin intake in rats are dependent not only upon the dose available for self-administration, but upon the session time and training dose as well.
在本研究中，使用大鼠自我给药模型来检验训练剂量和给药时段时间对海洛因剂量效应曲线的影响。与接受18微克/注射的动物相比，接受5.4微克/注射训练的动物中，低于5.4微克/注射的海洛因剂量能维持更高的药物摄取率。大于5.4微克/注射的剂量在两组动物中维持相似的摄取率。对于接受5.4微克/注射海洛因训练的动物，随着给药时段的推进，剂量反应曲线向下和向右移动；然而，当训练剂量为18微克/注射时，给药时段内剂量摄取曲线的移动则不太明显。对通过注射5.4微克海洛因引发反应的动物给予纳曲酮和纳曲吲哚，以确定这些拮抗剂在给药时段背景下的作用。在给药时段的4小时内，纳曲酮的效力下降，其时间进程与关于纳曲酮在大鼠脑中消除动力学的文献报道一致。相比之下，纳曲吲哚剂量与给药时段时间之间没有显著的相互作用。因此，大鼠的海洛因摄取率不仅取决于可用于自我给药的剂量，还取决于给药时段时间和训练剂量。
