Sex differences in the reduction of impulsive choice (delay discounting) for cocaine in rats with atomoxetine and progesterone.
Sex differences in the reduction of impulsive choice (delay discounting) for cocaine in rats with atomoxetine and progesterone.
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DOI：
10.1007/s00213-016-4345-3
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发表时间：
2016-08
影响因子：
3.4
通讯作者：
Carroll ME
中科院分区：
文献类型：
--
作者：
Smethells JR;Swalve NL;Eberly LE;Carroll ME
冲动的选择，或无法延迟即时满足，与药物滥用的发展和持续密切相关。事实上，推迟吸毒本身可能是吸毒成瘾和复吸的基础。因此，采用有效减少冲动选择（托莫西汀; ATO）或药物寻求行为（孕酮; PRO）的治疗可能是治疗药物成瘾的有效手段。本研究评估了PRO、ATO及其组合对可卡因和蔗糖颗粒的延迟贴现范例的影响的性别差异。雄性和雌性大鼠在蔗糖颗粒（1 vs 3颗粒）或静脉注射可卡因（0.3 vs 0.9 mg/kg）的冲动选择程序中选择小的立即或大的延迟（0，7.5，15，30，60秒）结果。在冲动选择的基线评估后，大鼠每天接受媒介物（VEH）、PRO（0.5 mg/kg）、ATO（1.5 mg/kg）或组合（PRO + ATO）的治疗，直到确定冲动选择的第二次评估。与VEH组相比，PRO或PRO + ATO联合治疗后女性对可卡因的冲动较低，而ATO后男性对可卡因的冲动较低。没有观察到对蔗糖颗粒的冲动选择的治疗效果。本研究结果表明，可卡因的冲动选择减少PRO在女性和ATO在男性。这些研究结果表明，这两种治疗方法可能是治疗可卡因滥用的有效干预措施，但其有效性因性别而异。
Impulsive choice, or an inability to delay immediate gratification, has been strongly linked to the development and persistence of drug abuse. Indeed, delaying drug use itself may underlie drug addiction and relapse. Thus, employing treatments that are efficacious in reducing impulsive choice (atomoxetine; ATO) or drug-seeking behavior (progesterone; PRO) may be an effective means of treating drug addiction. The current study assessed sex differences in the effects of PRO, ATO and their combination in a delay discounting paradigm for cocaine and for sucrose pellets. Male and female rats chose between a small-immediate or a large-delayed (0, 7.5, 15, 30, 60 sec) outcome in an impulsive choice procedure for sucrose pellets (1 vs 3 pellets) or for iv cocaine infusions (0.3 vs 0.9 mg/kg). Following baseline assessment of impulsive choice, rats received daily treatment of vehicle (VEH), PRO (0.5 mg/kg), ATO (1.5 mg/kg) or a combination (PRO + ATO) until a second assessment of impulsive choice was determined. Compared to the VEH group, females were less impulsive for cocaine following PRO or the PRO + ATO combined treatment, whereas males were less impulsive for cocaine following ATO. No treatment effects were observed on impulsive choice for sucrose pellets. The present results indicate that impulsive choice for cocaine is reduced by PRO in females and by ATO in males. These findings suggest both treatments may be an effective intervention in treating cocaine abuse, but that their effectiveness differs by sex.