University of Minnesota, Department of Psychiatry, MMC 392, 420 Delaware St SE, Minneapolis, MN 55455, USA.
Drug Alcohol Depend. 2010 Mar 1;107(2-3):264-7. doi: 10.1016/j.drugalcdep.2009.11.002. Epub 2009 Dec 14.
Sex differences exist in several aspects of cocaine abuse, and recent research suggests that this may be due, in part, to differential sensitivity to stress. Women, compared to men, exhibit greater stress-induced cocaine craving and responses to both cocaine and stress fluctuate during phases of the hormonal cycle. The goal of the present study was to compare male and female rats on the maintenance and extinction of cocaine seeking and on an animal model of stress-induced relapse by administering the pharmacological stressor yohimbine. An additional goal was to examine possible sex-specific treatment effects of the progesterone metabolite, allopregnanolone, on yohimbine-induced reinstatement. Male and female rats were trained to lever press for i.v. infusions of cocaine (0.4 mg/kg). Following a 14-day maintenance period, cocaine solutions were replaced with saline, and rats were allowed to extinguish lever pressing. Subsequently, rats were administered saline, yohimbine (2.5mg/kg), or allopregnanolone (15 mg/kg)+yohimbine (2.5mg/kg) priming injections on separate days using a within-subjects reinstatement procedure. The results indicated that females were more resistant to extinction than male rats and that both groups reinstated cocaine seeking following injections of yohimbine; however, female rats responded more than males to yohimbine-priming injections. Additionally, allopregnanolone blocked yohimbine's potentiating effect on responding in females but not males. These results suggest that females may be more sensitive than males to stress-induced reinstatement of cocaine-seeking behavior, and the progesterone metabolite, allopregnanolone, offers protection against this vulnerability.
性别的差异存在于可卡因滥用的几个方面，最近的研究表明，这可能部分归因于对压力的敏感性不同。与男性相比，女性表现出更大的应激诱导的可卡因渴望，并且对可卡因和应激的反应在激素周期的不同阶段波动。本研究的目的是比较雄性和雌性大鼠在可卡因寻求的维持和消退以及通过给予药理学应激源育亨宾的应激诱导复发的动物模型上的差异。另一个目的是研究孕激素代谢物孕烷醇酮对育亨宾诱导的复吸的可能性别特异性治疗效果。雄性和雌性大鼠被训练用于静脉内注射可卡因（0.4mg/kg）的杠杆按压。在 14 天的维持期后，用生理盐水替代可卡因溶液，让大鼠停止杠杆按压。随后，使用内被试重新激发程序，在不同天，分别给予大鼠生理盐水、育亨宾（2.5mg/kg）或孕烷醇酮（15mg/kg）+育亨宾（2.5mg/kg）的预注射。结果表明，雌性大鼠比雄性大鼠更能抵抗消退，并且两组大鼠在育亨宾注射后均重新开始可卡因寻求；然而，雌性大鼠对育亨宾预注射的反应比雄性大鼠更强烈。此外，孕烷醇酮阻断了育亨宾对雌性大鼠反应的增强作用，但对雄性大鼠没有作用。这些结果表明，女性可能比男性对应激诱导的可卡因寻求行为的复吸更为敏感，而孕激素代谢物孕烷醇酮提供了对这种脆弱性的保护。
