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阿托西班,一种催产素受体拮抗剂,可阻断雌性大鼠交配诱导的镇痛作用。

Copulation-induced antinociception in female rats is blocked by atosiban, an oxytocin receptor antagonist.

机构信息

Centro de Investigación en Reproducción Animal, Carlos Beyer, CINVESTAV-Universidad Autónoma de Tlaxcala, Panotla 90140, Apdo Postal 62, Mexico.

Centro de Investigación en Reproducción Animal, Carlos Beyer, CINVESTAV-Universidad Autónoma de Tlaxcala, Panotla 90140, Apdo Postal 62, Mexico.

出版信息

Horm Behav. 2019 Jan;107:76-79. doi: 10.1016/j.yhbeh.2018.12.001. Epub 2018 Dec 18.

Abstract

AIMS

We hypothesized that copulation-induced temporary anti-nociception in female rats is mediated by the activation of central and/or peripheral oxytocin receptors. To test this hypothesis, we assessed the effects of intraperitoneal (ip), intrathecal (it), and intra-cerebroventricular (icv) administration of an oxytocin receptor antagonist (atosiban), on copulation-induced temporary anti-nociception in estrous rats.

MAIN METHODS

The treatment groups were ovariectomized rats pre-treated subcutaneously (sc) with 10 μg of estradiol benzoate (EB) followed 24 h later by an sc injection of 5 μg EB, and 4 h later, by an sc injection of 2 mg progesterone (P4). Rats were then administered saline vehicle (ip, it, or icv: control groups) or atosiban (500 μg/kg ip; 500 ng it; or 500 ng icv: experimental groups). Thirty minutes after drug or saline administration, their sexual behavior was tested by pairing with a sexually-experienced male rat. Brief pulse trains of 50 Hz, 300 ms duration, supra-threshold tail electrical shocks (STS) were delivered before and during copulatory activity i.e., while the female was receiving mounts, intromissions, or ejaculations, and we recorded whether vocalization occurred in response to each STS.

KEY FINDINGS

Replicating our previous findings, the vocalization response to STS in control rats was significantly attenuated during intromissions and ejaculations, compared to their baseline (pre-mating) response, indicative of anti-nociception. By contrast, rats pre-treated with atosiban (each route of administration) failed to show an attenuation of the vocalization response to shock.

SIGNIFICANCE

These findings provide evidence that the temporary anti-nociceptive effect of copulation in female rats is mediated by copulation-induced release of endogenous oxytocin in brain, spinal cord and periphery.

摘要

目的

我们假设交配引起的雌性大鼠暂时镇痛是由中枢和/或外周催产素受体的激活介导的。为了验证这一假设,我们评估了腹腔内(ip)、鞘内(it)和脑室内(icv)给予催产素受体拮抗剂阿托西班(atosiban)对动情期大鼠交配引起的暂时镇痛的影响。

主要方法

实验组为经皮下(sc)预先给予 10μg苯甲酸雌二醇(EB)的去卵巢大鼠,24 小时后再给予 5μg EB 皮下注射,4 小时后给予 2mg 孕酮(P4)皮下注射。然后,大鼠接受生理盐水载体(ip、it 或 icv:对照组)或阿托西班(500μg/kg ip;500ng it;或 500ng icv:实验组)。给药或生理盐水 30 分钟后,通过与性经验丰富的雄性大鼠交配来测试它们的性行为。在交配活动期间,即当雌性接受交配、插入或射精时,给予 50Hz、300ms 时长、超阈值尾部电刺激(STS)的短暂脉冲串,并记录每次 STS 时是否发生发声。

主要发现

与我们之前的研究结果一致,与基线(交配前)反应相比,对照组大鼠对 STS 的发声反应在插入和射精期间明显减弱,表明有镇痛作用。相比之下,经阿托西班预处理的大鼠(每种给药途径)未能表现出对电击的发声反应减弱。

意义

这些发现为交配引起的雌性大鼠暂时镇痛效应是由大脑、脊髓和外周的内源性催产素释放介导提供了证据。

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