Department of Biomedical Sciences, Section of Neuroscience and Reproductive Biology, Tufts University, Cummings School of Veterinary Medicine, 200 Westboro Rd., North Grafton, MA 01536 USA.
Neurosci Lett. 2011 Sep 20;502(3):168-72. doi: 10.1016/j.neulet.2011.07.035. Epub 2011 Jul 30.
Recent studies have supported the hypothesis that pregnancy and parturition are associated with altered sensitivity of brain dopamine systems. An increased behavioral sensitivity to a direct-acting D1/D2 receptor agonist (apomorphine) has also been observed several weeks after lactation, suggesting that these adaptations are long-lasting. To further characterize this phenomenon, the effects of reproductive experience on behavioral sensitization to an indirect-acting dopamine agonist (amphetamine) in female rats were studied. In two separate experiments, nulliparous and primiparous (12-16 weeks post-weaning) female rats were pretreated with amphetamine (1.0 or 5.0mg/kg) or vehicle (saline) once daily for 5 consecutive days. After 10 days of withdrawal, all animals were challenged with a low dose of amphetamine (25% of pretreatment dose). Locomotor activity was measured following each drug or vehicle administration. Locomotor sensitization to amphetamine challenge was observed in all animals pretreated with 1mg/kg, regardless of reproductive experience. In contrast, primiparous animals pretreated with 5mg/kg amphetamine displayed a significantly larger locomotor response to the challenge compared to nulliparous controls. The findings indicate enhanced behavioral sensitization to amphetamine in reproductively experienced rats, and confirm previous reports of lasting adaptations of dopamine systems following pregnancy and lactation.
最近的研究支持了这样一种假设，即妊娠和分娩与大脑多巴胺系统敏感性的改变有关。在哺乳期后几周，也观察到对直接作用的 D1/D2 受体激动剂（阿扑吗啡）的行为敏感性增加，这表明这些适应性是持久的。为了进一步描述这种现象，研究了生殖经验对雌性大鼠间接作用的多巴胺激动剂（安非他命）行为敏化的影响。在两个单独的实验中，未产和初产（断奶后 12-16 周）的雌性大鼠每天用安非他命（1.0 或 5.0mg/kg）或载体（盐水）预处理一次，连续 5 天。停药 10 天后，所有动物均用低剂量安非他命（预处理剂量的 25%）进行挑战。每次给予药物或载体后测量运动活动。用 1mg/kg 预处理的所有动物均观察到对安非他命挑战的运动敏化，而无论其生殖经验如何。相比之下，用 5mg/kg 安非他命预处理的初产动物对挑战的运动反应明显大于未产对照动物。研究结果表明，在有生殖经验的大鼠中，对安非他命的行为敏化增强，并证实了先前关于妊娠和哺乳后多巴胺系统持久适应性的报告。
