Effects of estradiol on cocaine self-administration and cocaine discrimination by female rhesus monkeys.
Effects of estradiol on cocaine self-administration and cocaine discrimination by female rhesus monkeys.
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雌二醇对雌性恒河猴可卡因自我给药和可卡因辨别的影响。
DOI：
10.1038/sj.npp.1301451
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Mendelson,JackH
中科院分区：
文献类型：
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作者：
Mello,NancyK;Negus,SStevens;Knudson,IngeM;Kelly,Maureen;Mendelson,JackH
卵巢类固醇激素雌二醇在一定条件下可增强可卡因对啮齿动物的增强和运动激活作用。本研究评价了苯甲酸雌二醇酯(E2-β)对雌性恒河猴可卡因自我给药和辨别可卡因的急性影响。可卡因自身给药(0.10 mg/kg/inj，iv)维持在固定比例(FR)30的强化时间表上，猴子每天可以在一次2小时的疗程中获得可卡因。E2β在环糊精载体中(0.00001-0.0 1 mg/kg，im)，在每周两次试验前30min给予。在每次量效曲线测定(0.001-0.3 mg/kg/inj)过程中，可卡因剂量的给药顺序是不规律的。测试结束后采集血液样本，以确定17个β-雌二醇水平。香蕉味的食物颗粒按照FR 30时间表每天提供三次1小时的疗程。用两键食物强化法训练5只猴子辨别可卡因(0.1 8 mg/kg，im)和生理盐水，并研究了在环糊精和芝麻油中用E2β预处理的效果。与生理盐水对照组相比，急性给予E2β不会持续改变可卡因自身给药或药物辨别剂量-效应曲线。雌鼠也没有在生理盐水水平以上自行注射E2β(0.00001-0.10 mg/kg，iv)。最后，在训练为区分可卡因和生理盐水的猴子中，E2β(0.0001.0 5~0.0 1 mg/kg，im)不能替代可卡因。综上所述，这些数据表明，在所研究的剂量范围内，雌二醇的应用并不能始终如一地改变可卡因对雌性恒河猴的滥用相关影响。
The ovarian steroid hormone, estradiol, enhances the reinforcing and locomotor activating effects of cocaine in rodents under some conditions. The present study evaluated the acute effects of estradiol benzoate (E 2 β) on cocaine self-administration and cocaine discrimination in female rhesus monkeys. Cocaine self-administration (0.10 mg/kg/inj., iv) was maintained on a fixed-ratio (FR) 30 schedule of reinforcement, and monkeys had access to cocaine during one 2-h session each day. E 2 β in a cyclodextrin vehicle (0.00001–0.01 mg/kg, im) was administered 30 min before test sessions conducted twice each week. Cocaine doses were administered in an irregular order during each dose–effect curve determination (0.001–0.3 mg/kg/inj.). Blood samples were collected after test sessions to determine 17β-estradiol levels. Banana-flavored food pellets were available on an FR 30 schedule in three 1-h sessions each day. Five monkeys were trained to discriminate cocaine (0.18 mg/kg, im) from saline in a two-key food-reinforced procedure, and the effects of pretreatment with E 2 β in cyclodextrin and in sesame oil were studied. Acute administration of E 2 β did not consistently alter the cocaine self-administration or drug discrimination dose–effect curves in comparison to saline control treatment. Females also did not self-administer E 2 β (0.00001–0.10 mg/kg, iv) above saline levels. Finally, E 2 β (0.0001–0.01 mg/kg, im) did not substitute for cocaine in monkeys trained to discriminate cocaine from saline. Taken together, these data suggest that over the dose range studied, estradiol administration does not consistently alter the abuse-related effects of cocaine in female rhesus monkeys.