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产前甲基苯丙胺暴露和其他药物挑战剂量对成年大鼠行为影响的性别差异。

Gender differences in the effect of prenatal methamphetamine exposure and challenge dose of other drugs on behavior of adult rats.

机构信息

Department of Normal, Pathological and Clinical Physiology, Third Faculty of Medicine, Prague, Czech Republic.

出版信息

Physiol Res. 2013;62(Suppl 1):S99-S108. doi: 10.33549/physiolres.932593.

DOI:10.33549/physiolres.932593
PMID:24329709
Abstract

The aim of the present study was to compare the response to acute application of several drugs in adult male and female rats prenatally exposed to methamphetamine (MA). Spontaneous locomotor activity and exploratory behavior of adult male and female rats prenatally exposed to MA (5 mg/kg) or saline were tested in a Laboras apparatus (Metris B.V., Netherlands) for 1 h. Challenge dose of the examined drug [amphetamine - 5 mg/kg; cocaine - 5 mg/kg; MDMA (3,4-methylenedioxymethamphetamine) - 5 mg/kg; morphine - 5 mg/kg; THC (delta9-tetrahydrocannabinol) - 2 mg/kg] or saline was injected prior to testing. Our data demonstrate that prenatal MA exposure did not affect behavior in male rats with cocaine or morphine treatment, but increased locomotion and exploration in females. Application of amphetamine and MDMA in adulthood increased activity in both sexes, while cocaine and THC only in female rats. Morphine, on the other hand, decreased the activity in the Laboras test in both sexes. As far as sex and estrous cycle is concerned, the present study shows that males were generally less active than females and also females in proestrus-estrus phase of the estrous cycle were more active than females in diestrus. In conclusion, the present study shows that the prenatal MA exposure does not induce general sensitization but affects the sensitivity to drugs dependently to mechanism of drug action and with respect to gonadal hormones.

摘要

本研究旨在比较几种药物在成年雄性和雌性孕鼠暴露于甲基苯丙胺(MA)前后急性应用的反应。在 Laboras 仪器(Metris B.V.,荷兰)中,对孕鼠(5mg/kg)或生理盐水暴露的成年雄性和雌性大鼠进行 1 小时的自发性运动活动和探索行为测试。在测试前,注射检查药物的挑战剂量[安非他命-5mg/kg;可卡因-5mg/kg;MDMA(3,4-亚甲基二氧基甲基苯丙胺)-5mg/kg;吗啡-5mg/kg;THC(Δ9-四氢大麻酚)-2mg/kg]或生理盐水。我们的数据表明,孕鼠 MA 暴露不会影响雄性大鼠可卡因或吗啡治疗后的行为,但会增加雌性大鼠的运动和探索。成年后应用安非他命和 MDMA 会增加两性的活动,而可卡因和 THC 仅在雌性大鼠中增加。另一方面,吗啡会降低 Laboras 试验中两性的活动。就性别和发情周期而言,本研究表明雄性大鼠通常比雌性大鼠活动量少,而在发情周期的发情前期和发情期的雌性大鼠比发情后期的雌性大鼠活动量多。总之,本研究表明,孕鼠 MA 暴露不会引起普遍敏化,但会根据药物作用机制和性腺激素的不同而影响对药物的敏感性。

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