Carroll Marilyn E, Anderson Marissa M, Morgan Andrew D
Department of Psychiatry, University of Minnesota, MMC 392, Minneapolis, MN 55455, United States.
Pharmacol Biochem Behav. 2007 Nov;88(1):94-104. doi: 10.1016/j.pbb.2007.07.010. Epub 2007 Jul 25.
Rats selectively bred for high saccharin consumption (HiS) self-administer more oral ethanol and i.v. cocaine than those selectively bred for low saccharin consumption (LoS). Male and female drug-seeking-prone (HiS) and -resistant (LoS) rats were used in the present experiment to test the prediction that cocaine-induced locomotor activity and sensitization varied with sex and their selective breeding status (HiS and LoS). All rats were intermittently exposed over 2 weeks to pairs of sequential saline and cocaine injections, separated by 45 min. The first 5 pairs of injections, each separated by 2-3 days (10-12 days total), were given to examine the development of cocaine-induced locomotor activity and the development of locomotor sensitization, which was determined by comparing the effects of cocaine injection 1 with injection 6 (given 2 weeks after the 5 pairs of intermittent injections). Results indicated that after the first injection pair (saline, cocaine) the HiS and LoS groups did not differ (saline vs. cocaine) in locomotor activity; however, after cocaine injection pairs 1, 5, and 6, HiS females were more active than HiS males and LoS females. There were also significant phenotype differences (HiS>LoS) in locomotor activity after cocaine injections 5 and 6. There was a weak sensitization effect in cocaine-induced locomotor activity in HiS females after cocaine injection 5 (compared to 1); however it was not present after injection 6 or in other groups. The lack of a strong sensitization effect under these temporal and dose conditions was inconsistent with previous reports. However, the results showing HiS>LoS and females>males on cocaine-induced activity measures are consistent with several measures of cocaine-seeking behavior (acquisition, maintenance, escalation, extinction, and reinstatement), and they suggest that cocaine-induced locomotor activity and sensitization are behavioral markers of drug-seeking phenotypes.
选择性培育出的高糖精摄入量（HiS）大鼠比低糖精摄入量（LoS）大鼠能自我摄入更多的口服乙醇和静脉注射可卡因。在本实验中，使用了易寻求药物（HiS）和抗药物（LoS）的雄性和雌性大鼠，以检验可卡因诱导的运动活动和敏化作用随性别及其选择性育种状态（HiS和LoS）而变化的预测。所有大鼠在2周内间歇性地接受生理盐水和可卡因注射对，每次注射间隔45分钟。前5对注射，每对间隔2 - 3天（共10 - 12天），用于检查可卡因诱导的运动活动的发展以及运动敏化的发展，运动敏化通过比较第1次可卡因注射与第6次注射（在5对间歇性注射2周后给予）的效果来确定。结果表明，在第一对注射（生理盐水、可卡因）后，HiS组和LoS组在运动活动方面没有差异（生理盐水与可卡因）；然而，在第1、5和6次可卡因注射后，HiS雌性大鼠比HiS雄性大鼠和LoS雌性大鼠更活跃。在第5和6次可卡因注射后，运动活动也存在显著的表型差异（HiS>LoS）。在第5次可卡因注射后（与第1次相比），HiS雌性大鼠的可卡因诱导的运动活动有微弱的敏化作用；然而在第6次注射后或其他组中不存在这种情况。在这些时间和剂量条件下缺乏强烈的敏化作用与先前的报告不一致。然而，在可卡因诱导的活动测量中显示HiS>LoS以及雌性>雄性的结果与几种可卡因寻求行为的测量结果（获取、维持、升级、消退和恢复）一致，并且表明可卡因诱导的运动活动和敏化是药物寻求表型的行为标志物。
