Instituto de Investigación Médica M. y M. Ferreyra (INIMEC-CONICET), 5016 Córdoba, Argentina.
Physiol Behav. 2010 Aug 4;101(1):153-60. doi: 10.1016/j.physbeh.2010.04.033. Epub 2010 May 6.
The present study tested the involvement of the opioid system in the acquisition and expression of prenatal ethanol-related memories. We evaluated how this prenatal experience modulates ethanol self-administration in newborn rats, and preweanling's ingestion of the drug. During Gestational Days (GDs) 17-20, four groups of dams were treated with ethanol (2 g/kg) or water, followed immediately by naloxone (10 mg/kg) or saline administration. A fifth group received a similar dose of naloxone 20min before ethanol administration. On PD 1, pups were tested on an operant learning procedure to obtain milk or 3% ethanol. One hour later, an extinction session was performed. At Postnatal Days (PDs) 14 and 15, preweanlings representing each prenatal treatment were evaluated in an intake test with infusions of 5% ethanol or water. Prior to the intake test on PD14, preweanlings were administered naloxone (1 mg/kg), saline or remained untreated. In both tests, animals representative of both genders were utilized. One-day-old pups rapidly learned the operant behavior to gain access to milk. In contrast, only pups prenatally treated with ethanol (administered immediately before naloxone or saline injection) increased operant responding to gain access to ethanol. On an intake test at PDs 14 and 15, those animals prenatally exposed to naloxone 20 min before ethanol administration consumed significantly lower ethanol levels than the remaining prenatal ethanol groups. Postnatal treatment with naloxone diminished intake of all solutions at PD14. These results suggest that prenatal ethanol exposure facilitates neonatal operant learning reinforced by intraoral administration of ethanol and increases ethanol consumption during PDs 14-15. The endogenous opioid system apparently is involved in the acquisition of prenatal ethanol memories, which can modulate the reinforcing attributes of the drug in neonatal and preweanling rats.
本研究旨在检验阿片系统在产前乙醇相关记忆的获得和表达中的作用。我们评估了这种产前经历如何调节新生大鼠的乙醇自我给药，以及新生期对药物的摄入。在妊娠第 17-20 天，四组孕鼠接受乙醇（2g/kg）或水治疗，随后立即给予纳洛酮（10mg/kg）或生理盐水处理。第五组孕鼠在给予乙醇前 20 分钟接受相同剂量的纳洛酮处理。在生后第 1 天（PD1），幼鼠接受操作性学习程序以获得牛奶或 3%乙醇。1 小时后，进行消退程序。在 PD14 和 PD15，每个产前处理的幼鼠在 5%乙醇或水输注的摄入测试中进行评估。在 PD14 的摄入测试前，幼鼠给予纳洛酮（1mg/kg）、生理盐水或未处理。在这两个测试中，利用了来自两个性别的动物代表。1 天龄的幼鼠迅速学会了操作行为以获得牛奶。相比之下，只有在产前接受乙醇处理（在纳洛酮或生理盐水注射前立即给予）的幼鼠增加了操作反应以获得乙醇。在 PDs14 和 PD15 的摄入测试中，那些在产前给予纳洛酮 20 分钟后接受乙醇处理的动物摄入的乙醇水平明显低于其他产前乙醇组。在 PD14 时给予纳洛酮处理，会减少所有溶液的摄入。这些结果表明，产前乙醇暴露促进了新生大鼠通过口腔内给予乙醇的操作性学习，增加了 PDs14-15 期间的乙醇消耗。内源性阿片系统显然参与了产前乙醇记忆的获得，这可以调节新生和幼鼠对药物的强化属性。
