Interactions between progesterone and cocaine in women

月经周期中卵巢激素的变化会影响女性对可卡因的反应。研究表明，在月经周期的黄体期，当雌激素和孕酮浓度较高时，对可卡因的反应会减弱，而在月经周期的其他阶段，这些激素的浓度相对较低。我们假设对可卡因的减弱反应的基础是孕酮的多巴胺拮抗剂作用。作为证实我们假设的第一步，拟议的研究将检验外源性黄体酮单独和与雌激素联合使用对女性对吸烟可卡因的主观和生理反应的影响。外源性黄体酮和雌激素将在卵泡期注射，这将使我们能够相对不受可能与内源性激素相互作用的影响来检验它们的影响。在这份修订后的申请中，提出了两项研究。第一项研究将是一项受试者内和受试者之间的混合安慰剂对照住院研究，旨在表征0、200毫克和400毫克微粒化黄体酮对36名吸食可卡因的女性的安慰剂、0.2毫克/千克和0.4毫克/千克吸食可卡因的反应和自我管理的影响。第二项研究也将是一项受试者内部和受试者之间的混合实验(N=36)，在此实验中，将评估女性可卡因滥用者在孕酮(由实验1确定的剂量)和雌激素(0，0.05 mg/天和0.10 mg/天)预处理后对可卡因的反应。单独使用雌激素的影响也将被研究。我们预测黄体酮将减弱，而雌激素将增强对可卡因的反应，此外，我们预计在雌激素存在的情况下，黄体酮的影响可能会更明显。这些研究的结果综合在一起，有望深入了解月经周期阶段的基础，也许还有性别差异对可卡因反应的影响，并可能与针对女性可卡因滥用者的治疗方法的开发有关。

Changes in ovarian hormones across the menstrual cycle can impact upon responses to cocaine in women. Studies have shown that responses to cocaine are dampened during the luteal phase of the menstrual cycle, when estrogen and progesterone concentrations are high, relative to the other phases of the cycle, when concentrations of these hormones are relatively low. We have posited that the basis for attenuated responses to cocaine is the dopamine-antagonist effects of progesterone. As a first step to confirming our hypothesis, the proposed studies will examine the effects of exogenously administered progesterone, alone and in combination with estrogen, on subjective and physiological responses to smoked cocaine in women. Exogenous progesterone and estrogen will be administered during the follicular phase, which will enable us to examine their effects relatively unconfounded by possible interactions with endogenous hormones. Two studies are being proposed in this revised application. The first study will be a mixed within- and between-subjects, placebo-controlled inpatient study designed to characterize the effects of 0, 200 mg and 400 mg micronized progesterone on responses to and self-administration of placebo, 0.2 mg/kg and 0.4 mg/kg smoked cocaine in 36 women who abuse cocaine. The second study will also be a mixed within- and between-subjects experiment (N=36), in which responses to cocaine will be evaluated after pretreatment with progesterone (dose determined by Experiment 1) in combination with estrogen (0, 0.05 mg/day and 0.10 mg /day) in female cocaine abusers. The effects of estrogen alone will also be studied. We predict that progesterone will attenuate and estrogen will enhance responses to cocaine, and furthermore expect that the effects of progesterone may be more apparent in the presence of estrogen. The results of these studies, taken together, are expected to provide insight into the basis of menstrual cycle phase and perhaps gender differences on responses to cocaine, and may be relevant to the development of treatments targeted to female cocaine abusers.