Effects of Sex and Estrous Cycle on the Time Course of Incubation of Cue-Induced Craving following Extended-Access Cocaine Self-Administration.
Effects of Sex and Estrous Cycle on the Time Course of Incubation of Cue-Induced Craving following Extended-Access Cocaine Self-Administration.
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DOI：
10.1523/eneuro.0054-21.2021
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发表时间：
2021-07-01
期刊：
影响因子：
3.4
通讯作者：
Loweth, Jessica A
中科院分区：
文献类型：
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作者：
Corbett, Claire M;Dunn, Emily;Loweth, Jessica A
可卡因成瘾是一种毁灭性的公共卫生流行病，而且还在持续增长。重点研究确定影响可卡因渴望和复吸易感性的生物因素，对于促进戒毒者康复是必要的。众所周知，性激素和卵巢激素会影响人类和啮齿动物的可卡因成瘾倾向和复吸率。先前的研究调查了在长期可卡因自我给药戒断期间发生的提示诱发的可卡因渴望的时间依赖性强化或“孵化”的性别差异，并确定了整个大鼠生殖周期（动情周期）的变化。与发情周期所有其他阶段的雌性大鼠（非发情雌性）相比，处于周期发情阶段（即排卵发生的阶段）的雌性大鼠表现出孵化线索诱导的可卡因渴望程度的增加。在这里，我们通过评估早期戒断期（戒断第 1 和 15 天）和后期戒断期（戒断第 48 天）整个动情周期的孵化渴望来扩展这些发现。我们发现，发情期间（发情雌性）潜伏渴望程度的增加出现在停药第 15 天，但在停药第 1 天没有，并且在停药第 48 天进一步增加。在雄性和非发情雌性之间没有观察到潜伏渴望程度的差异。我们的数据表明，在戒断的第一个半月内，激素波动对提示引起的可卡因渴望的影响加剧，显示出戒断时间、动情周期波动和可卡因渴望之间的相互作用。
Cocaine addiction is a devastating public health epidemic that continues to grow. Studies focused on identifying biological factors influencing cocaine craving and relapse vulnerability are necessary to promote abstinence in recovering drug users. Sex and ovarian hormones are known to influence cocaine addiction liability and relapse vulnerability in both humans and rodents. Previous studies have investigated sex differences in the time-dependent intensification or "incubation" of cue-induced cocaine craving that occurs during withdrawal from extended-access cocaine self-administration and have identified changes across the rat reproductive cycle (estrous cycle). Female rats in the estrus stage of the cycle (Estrus Females), the phase during which ovulation occurs, show an increase in the magnitude of incubated cue-induced cocaine craving compared with females in all other phases of the estrous cycle (Non-Estrus Females). Here we extend these findings by assessing incubated craving across the estrous cycle during earlier withdrawal periods (withdrawal day 1 and 15) and later withdrawal periods (withdrawal day 48). We found that this increase in the magnitude of incubated craving during estrus (Estrus Females) is present on withdrawal day 15, but not on withdrawal day 1, and further increases by withdrawal day 48. No difference in the magnitude of incubated craving was observed between Males and Non-Estrus Females. Our data indicate that the effects of hormonal fluctuations on cue-induced cocaine craving intensify during the first month and a half of withdrawal, showing an interaction among abstinence length, estrous cycle fluctuations, and cocaine craving.