Carroll M E, Lac S T
Department of Psychiatry, University of Minnosota Medical School, Minneapolis 55455, USA.
Psychopharmacology (Berl). 1997 Feb;129(3):206-14. doi: 10.1007/s002130050182.
The effect of dose on the acquisition of i.v. amphetamine and cocaine self-administration was examined. Three unit doses of amphetamine (0.03, 0.06 and 0.12 mg/kg) and three unit doses of cocaine (0.05, 0.2 and 0.8 mg/kg) were tested in separate groups of ten (amphetamine) or 13 (cocaine) rats. Autoshaping methods were used to train rats to press a lever that resulted in drug infusion under a fixed-ratio (FR) 1 schedule. A daily 6-h autoshaping component non-contingently delivered 60 infusions according to a 60-s random time schedule with ten infusions delivered during the first half of each h. Each day autoshaping sessions were followed by a 6-h self-administration session. The criterion for acquisition was a 5-day period during which a daily mean of 100, 50 or 25 infusions for the three amphetamine doses and 400, 100 or 25 infusions were earned during the 6-h self-administration period for the three cocaine doses, respectively. As dose increased, more rats per group acquired drug self-administration and the mean number of days to meet the acquisition criterion decreased. The percentage of rats acquiring amphetamine self-administration increased with dose and ranged from 80 to 100%. Only one rat at the lowest cocaine dose met the acquisition criterion, but 100 percent of the rats at the two higher doses acquired. During the last 2 days of acquisition, mean infusions decreased and mean drug intake (mg/kg) increased as dose increased. On the last day of acquisition, the time course of infusions during the 6-h self-administration component was characterized by a steady rate of infusions per hour, and number of infusions was inversely related to dose. These findings indicate that the initial available dose of a drug is an important determinant of the rate and probability that successful acquisition will occur.
研究了剂量对静脉注射苯丙胺和可卡因自我给药习得的影响。分别对三组（每组10只用于苯丙胺实验或13只用于可卡因实验）大鼠测试了三个单位剂量的苯丙胺（0.03、0.06和0.12毫克/千克）和三个单位剂量的可卡因（0.05、0.2和0.8毫克/千克）。采用自动成型方法训练大鼠按压杠杆，按固定比率（FR）1的程序给药。每天6小时的自动成型环节按照60秒的随机时间表非连续地给予60次输注，每小时的前半小时给予10次输注。每天自动成型环节之后是6小时的自我给药环节。习得的标准是连续5天，三种苯丙胺剂量在6小时自我给药期间每天平均获得100次、50次或25次输注，三种可卡因剂量分别为400次、100次或25次输注。随着剂量增加，每组中更多的大鼠习得药物自我给药，达到习得标准的平均天数减少。习得苯丙胺自我给药的大鼠百分比随剂量增加，范围从80%到100%。最低可卡因剂量组只有一只大鼠达到习得标准，但较高剂量组的100%大鼠都达到了。在习得的最后2天，随着剂量增加，平均输注次数减少，平均药物摄入量（毫克/千克）增加。在习得的最后一天，6小时自我给药环节的输注时间进程的特点是每小时输注速率稳定，输注次数与剂量呈负相关。这些发现表明，药物的初始可用剂量是成功习得发生的速率和概率的重要决定因素。
