Ginsburg Brett C, Pinkston Jonathan W, Lamb Richard J
Department of Psychiatry, Division of Alcohol and Drug Addiction, The University of Texas Health Science Center at San Antonio, San Antonio 78229, USA.
Behav Pharmacol. 2012 Apr;23(2):134-42. doi: 10.1097/FBP.0b013e32834f9f9d.
The selective serotonin reuptake inhibitor fluvoxamine reduces responding for ethanol at lower doses than responding for food when each is available in separate components or separate groups of rats. However, when both are available concurrently and deliveries earned per session are equal, this apparent selectivity inverts and food-maintained behavior is more sensitive than ethanol-maintained behavior to rate-decreasing effects of fluvoxamine. Here, we investigated further the impact that concurrent access to both food and ethanol has on the potency of fluvoxamine. Fluvoxamine (5.6-17.8 mg/kg) potency was assessed under conditions in which food and ethanol were available concurrently and response rates were equal [average variable intervals (VIs) 405 and 14 s for food and ethanol, respectively], as well as when density of food delivery was increased (average VI 60 s for food and VI 14 s for ethanol). The potency of fluvoxamine was also determined when only ethanol was available (food extinction and average VI 14 s for ethanol) and under multiple VIs (VI 30 s for food and ethanol) wherein either food or ethanol was the only programmed reinforcement available during each component. Fluvoxamine was less potent at decreasing ethanol self-administration when food was available concurrently {ED50 [95% confidence limit (CL): 8.2 (6.5-10.3) and 10.7 (7.9-14.4)]} versus when ethanol was available in isolation [ED50: 4.0 (2.7-5.9) and 5.1 (4.3-6.0)]. Effects on food were similar under each condition in which food was available. The results demonstrate that the potency of fluvoxamine in reducing ethanol-maintained behavior depends on whether ethanol is available in isolation or in the context of concurrently scheduled food reinforcement.
在大鼠分别获取食物或乙醇的独立实验条件下,选择性5-羟色胺再摄取抑制剂氟伏沙明降低乙醇反应的剂量低于降低食物反应的剂量。然而,当食物和乙醇同时可得且每次实验获得的投放量相等时,这种明显的选择性会反转,食物维持行为比乙醇维持行为对氟伏沙明的降低反应率作用更敏感。在此,我们进一步研究了同时获取食物和乙醇对氟伏沙明效力的影响。在食物和乙醇同时可得且反应率相等的条件下(食物和乙醇的平均可变间隔分别为405秒和14秒),以及食物投放密度增加时(食物平均可变间隔为60秒,乙醇为14秒),对氟伏沙明(5.6 - 17.8毫克/千克)的效力进行了评估。当仅提供乙醇时(食物消退,乙醇平均可变间隔为14秒)以及在多重可变间隔条件下(食物和乙醇的可变间隔均为30秒,其中每个部分仅有一种强化物可供选择),也测定了氟伏沙明的效力。与单独提供乙醇相比,同时提供食物时氟伏沙明降低乙醇自我给药的效力较低{半数有效剂量[95%置信区间(CL):8.2(6.5 - 10.3)和10.7(7.9 - 14.4)]}[半数有效剂量:4.0(2.7 - 5.9)和5.1(4.3 - 6.0)]。在每种有食物可得的条件下,对食物的影响相似。结果表明,氟伏沙明降低乙醇维持行为的效力取决于乙醇是单独提供还是在同时安排食物强化的情况下提供。