Vathy I, Slamberová R, Liu Xinhe
Department of Psychiatry and Behavioral Sciences Albert Einstein College of Medicine, 1300 Morris Park Avenue, Ullmann Bldg., 111. Bronx, New York 10461, USA.
Dev Psychobiol. 2007 Jul;49(5):463-73. doi: 10.1002/dev.20240.
The present study was designed to investigate cocaine self-administration in adult male and female rats exposed prenatally to morphine. Pregnant dams were injected two times a day with either saline, analgesic doses of morphine or no drug at all (controls) on gestation Days 11-18. One day after birth, litters were cross-fostered such that control dams were paired with one another and their litters were crossed; saline- and morphine-treated dams were paired and half of each saline litter was crossed with half of each morphine litter. Thus, each mother (control, saline, and morphine) raised half of her own and half of the adopted litter. At the age of 60 days, males and females were trained first to lever press for sucrose pellets and then for cocaine. Once the lever-pressing behavior was learned and baseline level of this activity was established, animals received a cocaine (.5 mg/kg per infusion) reward for each correct response on the active lever during the next 9-day session. The data demonstrate that adult control, saline- and morphine-exposed male rats self-administer cocaine at a similar rate independent of their prenatal treatment. Adult female rats self-administer cocaine at a higher rate than male rats. Further, saline- and morphine-exposed females in diestrus self-administer more than females in proestrus phase of the estrous cycle, while control females show no such differences. In addition, fostering induces increase in cocaine self-administration in all groups of male rats regardless of prenatal drug exposure. In females, the only fostering-induced increase is in prenatally saline-exposed female rats raised by morphine-treated foster mother. Thus, our results suggest that the prenatal drug exposure does not induce changes in lever-pressing behavior for cocaine reward in adult male and female rats, but it sensitizes the animals to postnatal stimuli such as gonadal hormones and/or rearing conditions that result in increased drug self-administration.
本研究旨在调查成年雄性和雌性大鼠在产前暴露于吗啡后对可卡因的自我给药情况。在妊娠第11 - 18天,怀孕的母鼠每天注射两次,分别注射生理盐水、镇痛剂量的吗啡或不注射任何药物(对照组)。出生一天后,对幼崽进行交叉寄养,使对照组母鼠相互配对并交叉哺育它们的幼崽;注射生理盐水和吗啡的母鼠配对,每个生理盐水处理组幼崽的一半与每个吗啡处理组幼崽的一半进行交叉。因此,每只母鼠(对照组、生理盐水组和吗啡组)抚养自己幼崽的一半和领养幼崽的一半。60日龄时,雄性和雌性大鼠首先接受训练,按压杠杆以获取蔗糖颗粒,然后训练按压杠杆以获取可卡因。一旦学会杠杆按压行为并建立了该活动的基线水平,在接下来的9天实验中,动物每次在活动杠杆上做出正确反应都会获得可卡因(每次输注0.5mg/kg)奖励。数据表明,成年对照组、生理盐水处理组和吗啡处理组的雄性大鼠以相似的速率自我给药可卡因,与它们的产前处理无关。成年雌性大鼠自我给药可卡因的速率高于雄性大鼠。此外,处于动情间期的生理盐水处理组和吗啡处理组雌性大鼠比处于发情周期动情前期的雌性大鼠自我给药更多,而对照组雌性大鼠没有这种差异。此外,无论产前药物暴露情况如何,寄养都会导致所有雄性大鼠组的可卡因自我给药增加。在雌性大鼠中,唯一由寄养引起的增加是在由吗啡处理的寄养母鼠抚养的产前生理盐水处理组雌性大鼠中。因此,我们的结果表明,产前药物暴露不会诱导成年雄性和雌性大鼠对可卡因奖励的杠杆按压行为发生变化,但它使动物对产后刺激(如性腺激素和/或饲养条件)敏感,从而导致药物自我给药增加。