Department of Psychology, Washington State University Vancouver, 14204 NE Salmon Creek Ave, Vancouver, WA 98686, United States.
Department of Psychology, Washington State University Vancouver, 14204 NE Salmon Creek Ave, Vancouver, WA 98686, United States.
Behav Brain Res. 2024 Aug 24;472:115169. doi: 10.1016/j.bbr.2024.115169. Epub 2024 Jul 27.
Animal studies modeling recreational opioid use show more severe withdrawal symptoms in male compared to female rats, whereas our study modeling opioid use for pain showed a greater withdrawal-induced decrease in wheel running in female rats. The objective of this experiment was to determine whether sex differences in spontaneous morphine withdrawal are caused by differences in assessment method (i.e., wheel running vs. somatic symptoms). Twice daily injections of morphine (5 - 20 mg/kg, s.c.) for 5 days produced a dose and time dependent decrease in wheel running that was greater in male compared to female rats. Termination of morphine administration resulted in an overall decrease in running and a decrease in the amount of running during the dark phase of the light cycle from 95 % to approximately 75 %. In male rats, this decrease in the percent of dark running was caused by a large decrease in dark phase running, whereas female rats had a slightly higher increase in light phase running. Withdrawal also reduced maximal running speed and caused a decrease in body weight that was larger in male than female rats. Withdrawal symptoms were greatest on the day following the last morphine injection, but persisted for all 3 days of assessment. Morphine withdrawal produced a greater decrease in dark phase wheel running and body weight in male rats and a greater increase in light phase running in female rats. Voluntary home cage wheel running provides a continuous measure of opioid withdrawal that is consistent with other measures of opioid withdrawal.
动物研究模型表明，与雌性大鼠相比，雄性大鼠在娱乐性使用阿片类药物后会出现更严重的戒断症状，而我们的研究模型表明，在用于治疗疼痛的阿片类药物使用后，雌性大鼠的戒断引起的转轮运动减少更为明显。本实验的目的是确定自发吗啡戒断的性别差异是否是由评估方法（即转轮运动与躯体症状）的差异引起的。每天两次皮下注射吗啡（5-20mg/kg），连续 5 天，导致转轮运动呈剂量和时间依赖性减少，雄性大鼠比雌性大鼠更为明显。停止给予吗啡会导致总体转轮运动减少，以及从 95%减少到约 75%的光周期暗相转轮运动减少。在雄性大鼠中，这种暗相转轮运动减少的原因是暗相转轮运动的大幅减少，而雌性大鼠的光相转轮运动略有增加。戒断还降低了最大转轮速度，并导致雄性大鼠体重减轻，而雌性大鼠体重减轻幅度较大。戒断症状在最后一次吗啡注射后的第二天最为严重，但在所有 3 天的评估中仍持续存在。吗啡戒断导致雄性大鼠的暗相转轮运动和体重减少幅度更大，而雌性大鼠的亮相转轮运动增加幅度更大。自愿的笼内转轮运动提供了一种连续的阿片类药物戒断测量方法，与其他阿片类药物戒断测量方法一致。
