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多巴胺输注不会改变雌性恒河猴在慢性可卡因暴露前后的促黄体生成素水平。

Dopamine infusion does not alter LH levels before or after chronic cocaine exposure in female rhesus monkeys.

作者信息

Mello N K, Mendelson J H, Kelly M, Diaz-Migoyo N, Sholar J W

机构信息

Endocrine Unit, McLean Hospital, Belmont, MA 02178, USA.

出版信息

Pharmacol Biochem Behav. 1997 Nov;58(3):819-28. doi: 10.1016/s0091-3057(97)00042-7.

Abstract

Cocaine stimulates release of luteinizing hormone (LH) in preclinical and clinical studies but the contribution of the indirect dopamine agonist actions of cocaine to its effects on LH are unclear. In the present study, we examined the effects of exogenous dopamine infusions on LH release in drug-naive, normally cycling, female rhesus monkeys. All studies were conducted during the mid-follicular phase (cycle days 6-8). Three successive 80-min dopamine infusions (10 micrograms/kg/min, intravenous) were alternated with 20- or 40-min interruptions of dopamine infusions. There were no significant changes in LH during or following dopamine infusions. Predopamine baseline LH levels averaged 30 +/- 5.4 ng/ml. LH averaged 31.7 +/- 1.3 ng/ml during dopamine infusions and 31.4 +/- 1.3 ng/ml after dopamine infusions stopped. To determine whether chronic cocaine exposure influenced the effect of dopamine on LH, rhesus females were studied after more than 2 years of cocaine self-administration at an average dose of 6.5 +/- 0.2 mg/kg/day. LH averaged 27.3 +/- 3.3 ng/ml during baseline and 26.9 +/- 0.7 ng/ml and 26.1 +/- 0.7 ng/ml during dopamine infusions and interruptions, respectively. Similarly, during withdrawal from cocaine, baseline LH levels averaged 32.1 +/- 4.5 ng/ml, and LH did not change significantly during dopamine infusions (31.2 +/- 1.1 ng/ml) and infusion interruptions (32.1 +/- 1.1 ng/ml). Under the conditions of the present study, dopamine administration did not change LH levels in gonadally intact rhesus monkeys, and these findings are consistent with previous studies in ovariectomized rhesus females. However, these data are not consistent with clinical reports, and some possible implications of this species difference are discussed. Moreover, these data suggest that the stimulation of LH by cocaine may not be explained by its indirect dopamine agonist actions.

摘要

在临床前和临床研究中,可卡因可刺激促黄体生成素(LH)的释放,但可卡因的间接多巴胺激动剂作用对其LH效应的贡献尚不清楚。在本研究中,我们研究了外源性多巴胺输注对未接触过药物、正常月经周期的雌性恒河猴LH释放的影响。所有研究均在卵泡中期(月经周期第6 - 8天)进行。连续三次80分钟的多巴胺输注(10微克/千克/分钟,静脉注射)与20或40分钟的多巴胺输注中断交替进行。多巴胺输注期间或之后,LH没有显著变化。多巴胺输注前的基线LH水平平均为30±5.4纳克/毫升。多巴胺输注期间LH平均为31.7±1.3纳克/毫升,多巴胺输注停止后为31.4±1.3纳克/毫升。为了确定长期接触可卡因是否会影响多巴胺对LH的作用,对平均每天自我给药可卡因剂量为6.5±0.2毫克/千克、超过2年的恒河猴雌性进行了研究。基线时LH平均为27.3±3.3纳克/毫升,多巴胺输注期间平均为26.9±0.7纳克/毫升,输注中断期间平均为26.1±0.7纳克/毫升。同样,在可卡因戒断期间,基线LH水平平均为32.1±4.5纳克/毫升,多巴胺输注期间(31.2±1.1纳克/毫升)和输注中断期间(32.1±1.1纳克/毫升)LH没有显著变化。在本研究条件下,给予多巴胺不会改变性腺完整的恒河猴的LH水平,这些发现与先前对去卵巢恒河猴雌性的研究一致。然而,这些数据与临床报告不一致,并讨论了这种物种差异的一些可能影响。此外,这些数据表明,可卡因对LH的刺激作用可能无法用其间接多巴胺激动剂作用来解释。

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