Fontana D J, Commissaris R L
Department of Pharmaceutical Sciences, College of Pharmacy & AHP, Wayne State University, Detroit, MI 48202.
Life Sci. 1989;45(9):819-27. doi: 10.1016/0024-3205(89)90175-6.
The present studies examined the effects of acute cocaine administration, chronic cocaine administration and cocaine withdrawal on behavior in the Conditioned Suppression of Drinking (CSD) conflict paradigm, an animal model for the study of anxiety. In daily 10-minute sessions, water deprived rats were trained to drink from a tube that was occasionally electrified (0.25 mA), electrification being signalled by a tone. Within 3-4 weeks, control (i.e., non-drug) CSD behavior stabilized (30-50 shocks and 10-12 ml/session) and drug studies were initiated. Acute administration of cocaine (30-min pretreatment) produced a selective pro-conflict effect only at a dose of 10 mg/kg cocaine, with lower doses (2.5, 5 mg/kg) exerting no effect on CSD behavior and a higher dose (20 mg/kg) depressing both punished and unpunished responding. In a second experiment, cocaine (10 mg/kg, IP, 2/day) or saline was administered to separate groups of subjects for 7 weeks. In this chronic treatment study, CSD testing was conducted 12 hours after each evening cocaine administration. Although it had no effect on CSD behavior during the first week of treatment, this chronic cocaine administration produced a significant and selective pro-conflict effect which was stable during the period from Weeks 2-7. In a final experiment, a high dose of cocaine (20 mg/kg, 3/day) or saline was given to separate groups of subjects for 2 weeks and the behavioral effects of these treatments and their subsequent termination were examined. In this study, CSD testing was conducted 8 hours after each evening cocaine treatment. During the first week of high dose cocaine treatment, a decrease in punished responding was observed; this parameter returned to baseline levels by Week 2. Discontinuation of this high dose chronic cocaine treatment resulted in a selective decrease in punished responding. This pro-conflict effect was greatest at 3 days, and lasted for 6 days after the last cocaine dose. These data are consistent with clinical findings demonstrating the anxiogenic effects of both acute and chronic cocaine treatment as well as cocaine withdrawal and suggest that conflict paradigms such as the CSD may be useful for the study of cocaine-induced anxiety states.
本研究考察了急性给予可卡因、慢性给予可卡因以及可卡因戒断对条件性饮水抑制(CSD)冲突范式中行为的影响,该范式是一种用于研究焦虑的动物模型。在每天10分钟的实验时段中,剥夺水分的大鼠被训练从偶尔会通电(0.25毫安)的管子中饮水,通电由一个音调发出信号。在3 - 4周内,对照(即未用药)的CSD行为稳定下来(每次实验30 - 50次电击,饮水量10 - 12毫升),随后开始药物研究。急性给予可卡因(预处理30分钟)仅在剂量为10毫克/千克可卡因时产生选择性促冲突效应,较低剂量(2.5、5毫克/千克)对CSD行为无影响,而较高剂量(20毫克/千克)则抑制受惩罚和未受惩罚的反应。在第二个实验中,将可卡因(10毫克/千克,腹腔注射,每天2次)或生理盐水分别给予不同组的实验对象,持续7周。在这个慢性治疗研究中,每天晚上给予可卡因12小时后进行CSD测试。虽然在治疗的第一周对CSD行为没有影响,但这种慢性给予可卡因产生了显著的选择性促冲突效应,在第2 - 7周期间保持稳定。在最后一个实验中,将高剂量可卡因(20毫克/千克,每天3次)或生理盐水分别给予不同组的实验对象,持续2周,并考察这些处理及其随后终止的行为效应。在本研究中,每天晚上给予可卡因8小时后进行CSD测试。在高剂量可卡因治疗的第一周,观察到受惩罚反应减少;到第2周时该参数恢复到基线水平。停止这种高剂量慢性可卡因治疗导致受惩罚反应选择性降低。这种促冲突效应在第3天最大,并且在最后一剂可卡因后持续6天。这些数据与临床研究结果一致,表明急性和慢性可卡因治疗以及可卡因戒断均具有致焦虑作用,并提示诸如CSD这样的冲突范式可能有助于研究可卡因诱发的焦虑状态。