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，当雌激素和黄体酮浓度较高时，相对于周期的其他阶段，当这些激素浓度相对较低时，对可卡因的反应受到抑制。我们假设，对可卡因反应减弱的基础是黄体酮的多巴胺拮抗剂作用。作为证实我们假设的第一步，拟议的研究将检查外源性黄体酮单独或联合雌激素对女性吸食可卡因的主观和生理反应的影响。外源性孕酮和雌激素将在卵泡期给予，这将使我们能够检查它们的作用相对不受内源性激素可能相互作用的影响。修订后的申请中提出了两项研究。第一项研究将是一项混合受试者内部和受试者之间、安慰剂对照的住院研究，旨在描述0、200毫克和400毫克微孕酮对36名滥用可卡因的妇女对安慰剂、0.2毫克/公斤和0.4毫克/公斤吸烟可卡因的反应和自我给药的影响。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），其中将评估女性可卡因滥用者在使用黄体酮（实验1确定的剂量）联合雌激素（0,0.05 mg/天和0.10 mg/天）预处理后对可卡因的反应。单独雌激素的作用也将被研究。我们预测黄体酮将减弱而雌激素将增强对可卡因的反应，并且进一步预计黄体酮的作用在雌激素存在时可能更明显。这些研究的结果加在一起，可望深入了解月经周期阶段的基础以及对可卡因反应的性别差异，并可能与开发针对女性可卡因滥用者的治疗方法有关。

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.