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The influence of sex and estrous cyclicity on cocaine and remifentanil demand in rats

机译：性别和叙事循环对大鼠可卡因和雷芬内尼亚尔需求的影响

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Abstract The application of behavioral economic demand theory in addiction science has proved useful for evaluating individual characteristics underlying abuse liability. Two factors that have received comparably little attention within this literature are sex and gonadal hormones. We determined cocaine and remifentanil demand in male and female rats using a within‐session procedure. Cocaine and remifentanil demand were evaluated for 15 consecutive days using a balanced, crossover design that randomized drug order. This design allowed for the evaluation of temporal and exposure effects on two independent dimensions of demand, unconstrained demand ( Q 0 ) and demand elasticity ( α ). Estrous cyclicity was tracked to determine the contribution of phase to demand. No overall sex differences were observed. Increased unconstrained demand for cocaine and remifentanil was observed in females during periods in which estrogen was high (eg, estrus phase). Unconstrained remifentanil demand escalated over the 15‐day testing period, but escalation was not observed for cocaine or for demand elasticity. A significant exposure effect was also observed in which greater prior remifentanil intake increased unconstrained cocaine demand and reduced cocaine demand elasticity. These effects were directionally specific as no significant effects of prior cocaine exposure were observed on remifentanil demand measures. These data suggest that unconstrained demand and demand elasticity do not differ between male and female subjects; however, that unconstrained demand is associated with estrous cyclicity. These findings also suggest that opioid exposure enhances subsequent demand for psychomotor stimulants, which may be important when considering recent increases in nonmedical prescription opioid use in the United States.
机译：摘要行为经济需求理论在成瘾科学中的应用有助于评估滥用责任的个体特征。在这种文献中受到相对较少的两种因素是性和性腺激素。我们使用会话内程序确定了在雄性和女性大鼠中的可卡因和雷芬丹内尔。使用随机药物秩序的平衡的交叉设计，可随Cocaine和Remifentanil的需求连续15天进行评估。这种设计允许评估对需要的两个独立尺寸，无约束需求（Q 0）和需求弹性（α）的两个独立尺寸进行评估。跟踪了叙述性循环以确定阶段需求的贡献。没有观察到整体性别差异。在雌激素高（例如，雌激酶）的期间，在女性中观察到对可卡因和雷芬沙尼的不受约束需求增加。无约束的Remifentanil需求在15天测试期间升级，但可卡因或需求弹性未观察到升级。还观察到显着的暴露效果，其中更高的先前的雷芬丹尼尔进气量增加了无约束的可卡因需求和降低的可卡因需求弹性。这些效果在定向方向上，因为在雷芬丹内尔需求措施上没有观察到先前可卡因暴露的显着影响。这些数据表明，男女科目之间不受约束的需求和需求弹性不会有所不同;然而，不受约束的需求与叙述性循环相关。这些发现还表明阿片类药暴露可提高随后对精神刺激剂的需求，这在考虑最近在美国的非医疗处方阿片类药物的增加时可能是重要的。

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