Effects of progesterone and testosterone on cocaine self-administration and cocaine discrimination by female rhesus monkeys.
Effects of progesterone and testosterone on cocaine self-administration and cocaine discrimination by female rhesus monkeys.
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黄体酮和睾酮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/npp.2011.130
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发表时间：
2011
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;Knudson,IngeM;Kelly,Maureen;Fivel,PeterA;Mendelson,JackH
神经活性类固醇激素孕酮在某些情况下减弱了可卡因在女性和啮齿动物中的滥用相关影响，但睾酮的影响尚不清楚。我们比较了孕酮（0.1，0.2和0.3 mg/kg，肌肉注射（im）），睾酮（0.001，0.003和0.01 mg/kg，im）和安慰剂对可卡因自我给药和可卡因辨别剂量-效应曲线的急性效应。CO2自我给药（0.03 mg/kg/注射）维持在固定比率30的强化时间表上，并且猴子每天无限制地获得可卡因2小时。在每次剂量-效应曲线测定期间，以不规则的顺序给予考地平剂量，并且在所有治疗条件下，在每例受试者中使用相同的剂量顺序。在每次测试结束时收集用于激素分析的血液样品。香蕉味的食物颗粒（1克）也可在三个1小时的每日会议。在药物辨别实验中，研究了孕酮（0.032- 0.32mg/kg，im）和睾酮（0.001- 0.01mg/kg，im）预处理对可卡因（0.18mg/kg，im）辨别刺激效应的影响。孕酮和睾酮没有改变可卡因的歧视，并没有取代可卡因。相反，孕酮和睾酮各自显著降低可卡因自我给药，并在可卡因自我给药剂量效应曲线中产生向下和向下的偏移。这些发现与临床报告一致，孕酮给药可能会降低女性可卡因的积极主观影响的评级，并表明神经活性类固醇激素治疗可卡因滥用和降低复发风险的可能价值。
The neuroactive steroid hormone progesterone attenuates cocaine's abuse-related effects in women and in rodents under some conditions, but the effects of testosterone are unknown. We compared the acute effects of progesterone (0.1, 0.2, and 0.3 mg/kg, intramuscularly (im)), testosterone (0.001, 0.003, and 0.01 mg/kg, im), and placebo on cocaine self-administration and cocaine discrimination dose–effect curves in female rhesus monkeys. Cocaine self-administration (0.03 mg/kg per inj.) was maintained on a fixed ratio 30 schedule of reinforcement, and monkeys had unlimited access to cocaine for 2 h each day. Cocaine doses were administered in an irregular order during each dose–effect curve determination, and the same dose order was used in each subject in all treatment conditions. Blood samples for hormone analysis were collected at the end of each test session. Banana-flavored food pellets (1 g) were also available in three 1-h daily sessions. In drug discrimination studies, the effects of pretreatment with progesterone (0.032–0.32 mg/kg, im) and testosterone (0.001–0.01 mg/kg, im) on the discriminative stimulus effects of cocaine (0.18 mg/kg, im) were examined. Progesterone and testosterone did not alter cocaine discrimination, and did not substitute for cocaine. In contrast, progesterone and testosterone each significantly decreased cocaine self-administration, and produced a downward and rightward shift in the cocaine self-administration dose–effect curve. These findings are concordant with clinical reports that progesterone administration may decrease ratings of positive subjective effects of cocaine in women, and suggest the possible value of neuroactive steroid hormones for the treatment of cocaine abuse and reduction of risk for relapse.