Nizhnikov Michael E, Molina Juan Carlos, Varlinskaya Elena I, Spear Norman E
Department of Psychology, Center for Developmental Psychobiology, Binghamton University, Binghamton, NY 13902-6000, USA.
Alcohol Clin Exp Res. 2006 Jan;30(1):34-45. doi: 10.1111/j.1530-0277.2006.00009.x.
Recent experimental findings indicate that newborn rats are quite susceptible to the reinforcing properties of ethanol (EtOH). The basis seems to be more pharmacological than gustatory, olfactory, or caloric as a single pairing of a surrogate nipple providing water with an intraperitoneal (i.p.) injection of EtOH results in conditioned attachment to an empty surrogate nipple. The present study tested whether prenatal exposure to moderate EtOH during late gestation would alter the neonatal rat's susceptibility to this source of EtOH reinforcement and/or EtOH metabolism.
Pregnant females were given 1 g/kg EtOH or water intragastrically on gestational days (GD) 17 to 20 or were untreated. Rat pups delivered by cesarean section on GD 21 were exposed 3 to 4 hours later to a surrogate nipple providing water, either immediately following or 10 minutes before an i.p. injection of 0.0 (saline), 0.25, 0.5, or 0.75 g/kg EtOH (12.6%, v/v). Ethanol reinforcement was indicated by a significant increase in time attached to an empty surrogate nipple compared with unpaired and saline controls. Testing was conducted 90 minutes after conditioning took place. Blood ethanol levels (BELs) were also taken from subjects injected with identical doses of i.p. EtOH at 5 or 95 minutes after injection.
Initial response to a surrogate nipple with water did not differ between groups. For neonates prenatally exposed to EtOH, significant reinforcement by all 3 doses of i.p. EtOH (0.25, 0.5, and 0.75) was found, whereas only the dose of 0.5 g/kg EtOH was reinforcing for neonates in the prenatal water condition and only 0.25 g/kg was reinforcing for pups from untreated dams. Blood ethanol levels after conditioning also differed as a function of prenatal treatment.
These results suggest that prenatal EtOH exposure increases the range of EtOH doses capable of reinforcing effects. Intubations with water, however, eliminated the reinforcing strength of the lowest dose (0.25 g/kg) and shifted the dose-response curve to the right. This effect may be due to the stress of the intubation procedure. Ethanol metabolism was also affected by prenatal EtOH exposure. Pups derived from EtOH-treated dams had slower elimination of EtOH from the blood than all other groups at both the 0.5 and 0.75 g/kg i.p. doses.
最近的实验结果表明,新生大鼠对乙醇(EtOH)的强化特性相当敏感。其基础似乎更多是药理学方面的,而非味觉、嗅觉或热量方面的,因为将提供水的替代乳头与腹腔内(i.p.)注射EtOH单次配对,会导致对空替代乳头产生条件性依恋。本研究测试了妊娠晚期产前暴露于中度EtOH是否会改变新生大鼠对这种EtOH强化源的易感性和/或EtOH代谢。
在妊娠第17至20天,给怀孕的雌性大鼠灌胃1 g/kg EtOH或水,或者不进行处理。在妊娠第21天通过剖宫产分娩的幼鼠,在3至4小时后暴露于提供水的替代乳头,在腹腔注射0.0(生理盐水)、0.25、0.5或0.75 g/kg EtOH(12.6%,v/v)之前或之后立即进行。与未配对和生理盐水对照组相比,对空替代乳头的依恋时间显著增加表明有EtOH强化作用。在条件反射形成90分钟后进行测试。还在注射后5或95分钟从注射相同剂量腹腔内EtOH的受试者身上采集血液乙醇水平(BELs)。
各组对带有水的替代乳头的初始反应没有差异。对于产前暴露于EtOH的新生儿,发现所有3种腹腔内EtOH剂量(0.25、0.5和0.75)都有显著强化作用,而对于产前处于水条件下的新生儿,只有0.5 g/kg EtOH剂量有强化作用,对于未处理母鼠的幼崽,只有0.25 g/kg有强化作用。条件反射后的血液乙醇水平也因产前处理而有所不同。
这些结果表明,产前暴露于EtOH会增加能够产生强化作用的EtOH剂量范围。然而,用水插管消除了最低剂量(0.25 g/kg)的强化强度,并使剂量反应曲线向右移动。这种效应可能是由于插管过程的应激。EtOH代谢也受到产前EtOH暴露的影响。在0.5和0.75 g/kg腹腔内剂量下,来自EtOH处理母鼠的幼崽血液中EtOH的消除速度比所有其他组都慢。