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.

译文

我们以前已经表明,扩展访问对象在跑道模型中表现出对可卡因的动机增强,这反映在撤退次数减少的情况下。这种增强的动机可能反映出可卡因引起的奖励的增加或可卡因引起的厌恶情绪的减少。因此,当前的实验旨在使用位置条件测试来评估可卡因诱导的延长访问大鼠的奖赏和厌恶。训练的大鼠在10天内每天6小时接触药物,以静脉注射 (IV) 可卡因 (0.25毫克/输注)。对照受试者的杠杆按压可静脉输注盐水。在药物自我给药后,受试者对可卡因的即时或延迟作用 (1.0或2.5  mg/kg,IV) 进行了位置调节。在对照受试者中,低剂量可卡因的直接影响产生了条件偏好 (cpp),而延迟影响产生了条件厌恶 (cpa)。相反,接受低可卡因剂量6小时的动物表现出厌恶的地方,但没有偏好; 当可卡因剂量增加时,这种效果被逆转。此外,在6小时组中,延迟调节与内侧前额叶皮层和伏隔核壳中zif268免疫反应性降低有关,而立即调节与杏仁核中央核中zif268-positive细胞的增加有关。总的来说,这些数据表明,每天延长使用可卡因的时间会导致受试者感知的奖励阈值发生变化,而奖励和压力途径的活动也发生了变化。

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