Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA.
J Neuroendocrinol. 2012 Apr;24(4):701-11. doi: 10.1111/j.1365-2826.2012.02291.x.
The cycle of chronic cocaine (CC) use and withdrawal results in increased anxiety, depression and disrupted stress-responsiveness. Oxytocin and corticosterone (CORT) interact to mediate hormonal stress responses and can be altered by cocaine use. These neuroendocrine signals play important regulatory roles in a variety of social behaviours, specifically during the postpartum period, and are sensitive to disruption by CC exposure in both clinical settings and preclinical models. To determine whether CC exposure during pregnancy affected behavioural and hormonal stress response in the early postpartum period in a rodent model, Sprague-Dawley rats were administered cocaine daily (30 mg/kg) throughout gestation (days 1-20). Open field test (OFT) and forced swim test (FST) behaviours were measured on postpartum day 5. Plasma CORT concentrations were measured before and after testing throughout the test day, whereas plasma and brain oxytocin concentrations were measured post-testing only. The results obtained indicated increased CORT response after the OFT in CC-treated dams (P ≤ 0.05). CC-treated dams also exhibited altered FST behaviour (P ≤ 0.05), suggesting abnormal stress responsiveness. Peripheral, but not central, oxytocin levels were increased by cocaine treatment (P ≤ 0.05). Peripheral oxytocin and CORT increased after the FST, regardless of treatment condition (P ≤ 0.05). Changes in stress-responsiveness, both behaviourally and hormonally, may underlie some deficits in maternal behaviour; thus, a clearer understanding of the effect of CC on the stress response system may potentially lead to treatment interventions that could be relevant to clinical populations. Additionally, these results indicate that CC treatment can have long-lasting effects on peripheral oxytocin regulation in rats, similar to changes observed in persistent social behaviour and stress-response deficits in clinical populations.
慢性可卡因(CC)使用和戒断会导致焦虑、抑郁和应激反应失调增加。催产素和皮质酮(CORT)相互作用调节激素应激反应,可卡因的使用可以改变这些反应。这些神经内分泌信号在各种社会行为中发挥着重要的调节作用,特别是在产后期间,并且对 CC 暴露在临床环境和临床前模型中的破坏敏感。为了确定妊娠期 CC 暴露是否会影响产后早期的行为和激素应激反应,在一种啮齿动物模型中,给予 Sprague-Dawley 大鼠每日(30mg/kg)可卡因,直至妊娠第 20 天。在产后第 5 天测量旷场试验(OFT)和强迫游泳试验(FST)行为。在整个测试日,在测试前后测量血浆 CORT 浓度,而仅在测试后测量血浆和脑催产素浓度。结果表明,CC 处理的母鼠在 OFT 后 CORT 反应增加(P≤0.05)。CC 处理的母鼠还表现出 FST 行为改变(P≤0.05),表明应激反应异常。可卡因处理增加了外周而非中枢催产素水平(P≤0.05)。无论处理条件如何,FST 后外周催产素和 CORT 均增加(P≤0.05)。行为和激素应激反应的变化可能是某些母性行为缺陷的基础;因此,更清楚地了解 CC 对应激反应系统的影响可能会导致针对临床人群的治疗干预。此外,这些结果表明,CC 处理可以在大鼠中对外周催产素调节产生持久影响,类似于在临床人群中观察到的持久社会行为和应激反应缺陷变化。