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性别和月经周期对食蟹猴可卡因自我给药渐进比率测量的影响。

Sex and menstrual cycle effects on progressive ratio measures of cocaine self-administration in cynomolgus monkeys.

作者信息

Mello Nancy K, Knudson Inge M, Mendelson Jack H

机构信息

Alcohol and Drug Abuse Research Center, Harvard Medical School-McLean Hospital, 115 Mill Street, Belmont, MA 02478, USA.

出版信息

Neuropsychopharmacology. 2007 Sep;32(9):1956-66. doi: 10.1038/sj.npp.1301314. Epub 2007 Jan 24.

Abstract

Fluctuations in ovarian steroid hormones across the menstrual/estrous cycle influence the abuse-related effects of acute cocaine administration in women and chronic cocaine self-administration in rodents, but there have been no comparable studies in non-human primates. The interactions among sex, menstrual cycle phase, and cocaine self-administration (0.0032, 0.01, and 0.032 mg/kg/injection (inj)) under a progressive ratio schedule were investigated in four female and two male cynomolgus monkeys. Females were given unrestricted access to cocaine across 54 menstrual cycles, and males were studied over 23 pseudo-cycles of 30 days duration. Ovulatory cycles were defined by luteal phase elevations in progesterone and 44 cycles were ovulatory. During ovulatory menstrual cycles, females reached significantly higher progressive ratio break points than males at all three unit doses of cocaine (P<0.001). During anovulatory cycles, females also reached significantly higher break points than males for 0.032 mg/kg/inj cocaine (P<0.01). Progressive ratio break points for cocaine (0.01 and 0.032 mg/kg/inj) did not vary significantly as a function of ovarian steroid hormone levels during the follicular and the luteal phase of ovulatory menstrual cycles, or during anovulatory cycles. Progressive ratio break points for 0.0032 mg/kg/inj cocaine were significantly higher during the follicular phase than during the late luteal phase (P<0.05-0.001). There were no systematic changes in progressive ratio break points in male pseudo-cycles. Significant cocaine dose-related sex differences were observed, but no consistent changes in cocaine self-administration as a function of menstrual cycle phase, or levels of estradiol and progesterone, were detected in female cynomolgus monkeys.

摘要

整个月经/发情周期中卵巢甾体激素的波动会影响女性急性可卡因给药的成瘾相关效应以及啮齿动物的慢性可卡因自我给药,但在非人灵长类动物中尚未有类似研究。我们在4只雌性和2只雄性食蟹猴中研究了性别、月经周期阶段与可卡因自我给药(0.0032、0.01和0.032毫克/千克/注射)在累进比率程序下的相互作用。雌性在54个月经周期中可无限制获取可卡因,雄性在23个持续30天的假周期中接受研究。排卵周期通过黄体期孕酮升高来定义,其中44个周期为排卵周期。在排卵性月经周期中,在所有三个单位剂量的可卡因下,雌性达到的累进比率断点显著高于雄性(P<0.001)。在无排卵周期中,对于0.032毫克/千克/注射的可卡因,雌性达到的断点也显著高于雄性(P<0.01)。在排卵性月经周期的卵泡期和黄体期以及无排卵周期中,可卡因(0.01和0.032毫克/千克/注射)的累进比率断点并未随卵巢甾体激素水平发生显著变化。0.0032毫克/千克/注射可卡因的累进比率断点在卵泡期显著高于黄体晚期(P<0.05 - 0.001)。雄性假周期中的累进比率断点没有系统性变化。观察到显著的可卡因剂量相关性别差异,但在雌性食蟹猴中未检测到可卡因自我给药随月经周期阶段或雌二醇和孕酮水平的一致变化。

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