Su Zu-In, Wenzel Jennifer, Ettenberg Aaron, Ben-Shahar Osnat
Behavioral Pharmacology Laboratory, Department of Psychological and Brain Sciences, University of California, Santa Barbara, CA, USA.
Addict Biol. 2014 Sep;19(5):826-37. doi: 10.1111/adb.12053. Epub 2013 May 1.
We have previously shown that extended-access subjects exhibit heightened motivation for cocaine in the runway model, as reflected by reduced number of retreats. This heightened motivation could reflect either an increase in cocaine-induced reward or a decrease in cocaine-induced aversion. The current experiment was therefore devised to assess the cocaine-induced reward and aversion in extended-access rats using a place conditioning test. Rats trained to lever press for intravenous (IV) cocaine (0.25 mg/infusion) were provided 6-hour daily access to the drug over 10 days. Lever pressing in control subjects produced IV infusions of saline. Following drug self-administration, subjects underwent place conditioning for the immediate or delayed effects of cocaine (1.0 or 2.5 mg/kg, IV). In control subjects, the immediate effects of the low dose of cocaine produced conditioned places preferences (CPPs), while the delayed effects produced conditioned place aversions (CPAs). In contrast, the animals receiving low cocaine dose for 6 hours, exhibited place aversions but not preferences; an effect that was reversed when the dose of cocaine was increased. Additionally, in the 6-hour group, delayed conditioning was associated with a reduction in zif268 immunoreactivity in the medial prefrontal cortex and nucleus accumbens shell while immediate conditioning was associated with an increase in zif268-positive cells in the central nucleus of the amygdala. Collectively, these data suggest that extended daily access to cocaine produces a shift in the subject's perceived reward threshold that is paralleled by alterations in the activity of both the reward and stress pathways.
我们之前已经表明，在跑道模型中，长期接触可卡因的实验对象对可卡因的动机增强，这表现为退缩次数减少。这种增强的动机可能反映了可卡因诱导的奖赏增加，或者可卡因诱导的厌恶减少。因此，本实验旨在使用位置条件化测试评估长期接触可卡因的大鼠中可卡因诱导的奖赏和厌恶。训练大鼠按压杠杆以静脉注射（IV）可卡因（0.25毫克/次输注），并在10天内每天给予其6小时的药物接触时间。对照组大鼠按压杠杆会静脉注射生理盐水。在药物自我给药后，实验对象接受可卡因（1.0或2.5毫克/千克，静脉注射）即时或延迟效应的位置条件化。在对照组中，低剂量可卡因的即时效应产生了条件性位置偏好（CPPs），而延迟效应产生了条件性位置厌恶（CPAs）。相比之下，接受低剂量可卡因6小时的动物表现出位置厌恶而非偏好；当可卡因剂量增加时，这种效应会逆转。此外，在6小时组中，延迟条件化与内侧前额叶皮质和伏隔核壳中zif268免疫反应性降低有关，而即时条件化与杏仁核中央核中zif268阳性细胞增加有关。总体而言，这些数据表明，每天长时间接触可卡因会导致实验对象感知到的奖赏阈值发生变化，同时奖赏和应激途径的活动也会发生改变。
