Martin T J, Walker L E, Sizemore G M, Smith J E, Dworkin S I
Department of Physiology and Pharmacology, Bowman Gray School of Medicine, Winston-Salem, NC 27157-1083, USA.
Drug Alcohol Depend. 1996 Jun;41(2):93-100. doi: 10.1016/0376-8716(96)01245-8.
A procedure was employed in the present study to obtain dose-response curves for heroin self-administration within each experimental session. The data generated using this procedure were compared to dose-response data obtained using between-session dose manipulations. The dose of heroin (18, 30, 60 or 100 micrograms/kg/inf) was varied across 4-hourly segments separated by a 20-min time-out period during which heroin was not available. The within-session dose-response procedure yielded data similar to those obtained using between-session dose manipulations when the order of dose presentation was increasing or random. However, the dose-response curve for total drug-intake was flat when the doses were presented in decreasing order. Further analysis of the dose-response curves in the within-session procedure demonstrated that the rate of heroin intake increased in the third and fourth hourly components compared to the first component, suggesting acute tolerance to the reinforcing and/or rate-suppressive effects of heroin. Furthermore, using a random order of dose presentation, administration of 3.0 mg/kg of naltrexone prior to the session shifted the dose-response curve for heroin self-administration 5-fold to the right in the within-session procedure. The data indicate that the within-session dose-response procedure can be used to investigate the pharmacology of heroin self-administration in rodents.
本研究采用了一种程序来获取每个实验时段内海洛因自我给药的剂量-反应曲线。将使用该程序生成的数据与通过时段间剂量操作获得的剂量-反应数据进行比较。海洛因剂量（18、30、60或100微克/千克/注射）在每4小时的时间段内变化，各时间段之间有20分钟的休息期，在此期间无法获取海洛因。当剂量呈现顺序为递增或随机时，时段内剂量-反应程序产生的数据与通过时段间剂量操作获得的数据相似。然而，当剂量按递减顺序呈现时，总药物摄入量的剂量-反应曲线是平坦的。对时段内程序中的剂量-反应曲线进行进一步分析表明，与第一个小时段相比，海洛因摄入量在第三和第四个小时段有所增加，这表明对海洛因的强化和/或速率抑制作用产生了急性耐受性。此外，在时段内程序中，采用随机的剂量呈现顺序，在实验前给予3.0毫克/千克的纳曲酮，可使海洛因自我给药的剂量-反应曲线向右移动5倍。数据表明，时段内剂量-反应程序可用于研究啮齿动物中海洛因自我给药的药理学。
