Department of Pharmacology and Cancer Biology, Duke University Medical Center, Research Drive, Durham, NC 27710, USA.
Psychopharmacology (Berl). 2013 Feb;225(3):707-18. doi: 10.1007/s00213-012-2860-4. Epub 2012 Sep 14.
Women are more sensitive than men to psychostimulants and progress from initial use to drug addiction more quickly. The mouse has been an under-utilized model to study sex differences in psychostimulant action. Mice could serve as an ideal genetically tractable model for mechanistic studies into sex and hormone effects on psychostimulant behavior.
The objective of this study was to characterize psychostimulant effects in male and female mice with a combination of automated data collection and behavioral observation.
Male and female C57BL/6 mice (Charles River) were given a single dose or sequential ascending binge doses of D-amphetamine (AMPH) or cocaine (COC). Behavior was assessed in open field chambers using both automated photobeam interruptions and behavioral observations. Brain psychostimulant concentrations were determined at the time of maximum behavioral stimulation.
Psychostimulants induced behavioral activation in mice including both increased locomotion as detected with an automated system and a sequence of behaviors progressing from stereotyped sniffing at low doses to patterned locomotion and rearing at high doses. Females exhibited more patterned locomotion and a shift towards higher behavior scores after either psychostimulant despite having lower AMPH and equivalent COC brain levels as males.
Female C57BL/6 mice exhibit enhanced psychostimulant-induced behavior compared to males, similar to reports in rats. The combination of automated behavioral measures and behavioral observation was essential for verifying the existence of these differences. These results indicate the importance of testing both sexes when characterizing genetically manipulated mice to control for potential sex-specific effects.
女性对精神兴奋剂比男性更敏感，并且从最初使用到药物成瘾的进展速度比男性更快。老鼠一直是研究精神兴奋剂作用中性别差异的利用不足的模型。老鼠可以作为研究性和激素对精神兴奋剂行为影响的机制的理想遗传上可操作的模型。
本研究的目的是通过自动化数据收集和行为观察相结合的方法，描述雄性和雌性小鼠的精神兴奋剂作用。
雄性和雌性 C57BL/6 小鼠（Charles River）单次给予安非他命（AMPH）或可卡因（COC）递增剂量。使用自动光电中断和行为观察在开阔场室中评估行为。在行为最大刺激时测定脑内精神兴奋剂浓度。
精神兴奋剂诱导小鼠行为激活，包括自动系统检测到的运动增加，以及从低剂量的刻板嗅探到高剂量的模式运动和竖起行为的一系列行为进展。尽管雌性的 AMPH 和 COC 脑水平与雄性相当，但在两种精神兴奋剂后，雌性表现出更多的模式运动和更高的行为评分。
与大鼠的报告类似，雌性 C57BL/6 小鼠比雄性表现出增强的精神兴奋剂诱导的行为。自动化行为测量和行为观察的结合对于验证这些差异的存在至关重要。这些结果表明，在表征基因操作的小鼠时，测试两性都很重要，以控制潜在的性别特异性影响。
