Instituto de Investigación Médica M. y M. Ferreyra (INIMEC-CONICET), Córdoba, C.P. 5000, Argentina.
Behav Brain Res. 2011 Jan 1;216(1):262-9. doi: 10.1016/j.bbr.2010.08.005. Epub 2010 Aug 12.
Age-related differences in ethanol sensitivity could put adolescents at risk for developing alcohol-related problems. Little information exists, however, about adolescent sensitivity to ethanol's appetitive effects and the neurobiological mechanisms underlying ethanol reinforcement during this developmental stage. The present study assessed the role of the opioid system in adolescent rats in an appetitive second-order schedule of ethanol reinforcement and ethanol-induced locomotor stimulation. On postnatal day 32 (PD32), animals were pretreated with the general opioid antagonist naloxone (0.0, 0.75, 1.50, or 2.5 mg/kg) and then given pairings of ethanol (0.0 or 2.0 g/kg, intragastrically) with intraoral pulses of water (conditioned stimulus 1 [CS₁], first-order conditioning phase). CS₁ delivery occurred 30-45 min after ethanol administration when the effect of ethanol was assumed to be appetitive. On PD33, adolescents were exposed to CS₁ (second-order conditioning phase) while in a chamber featuring distinctive exteroceptive cues (CS₂). Preference for CS₂ was then tested. Adolescents given CS₁-ethanol pairings exhibited greater preference for CS₂ than controls, indicating ethanol-mediated reinforcement, but only when not pretreated with naloxone. Blood alcohol levels during conditioning were not altered by naloxone. Experiment 2 revealed that ethanol-induced locomotor activation soon after administration, and naloxone dose-dependently suppressed this stimulating effect. The present study indicates that adolescent rats are sensitive to ethanol's reinforcing and locomotor-stimulating effects. Both effects of ethanol appear to be mediated by endogenous opioid system activation.
年龄相关的乙醇敏感性差异可能使青少年面临发展为与酒精相关问题的风险。然而，关于青少年对乙醇的食欲效应的敏感性以及在这个发育阶段乙醇强化的神经生物学机制的信息很少。本研究评估了阿片系统在青少年大鼠中的作用，在乙醇强化的二级序贯时间表和乙醇诱导的运动刺激中。在出生后第 32 天（PD32），动物用通用阿片拮抗剂纳洛酮（0.0、0.75、1.50 或 2.5 mg/kg）预处理，然后用口腔内的水脉冲与乙醇（0.0 或 2.0 g/kg，胃内）配对（条件刺激 1 [CS₁]，第一级条件反射阶段）。当乙醇的作用被认为是食欲性时，CS₁的传递发生在乙醇给药后 30-45 分钟。在 PD33，青少年在具有独特的外感受线索（CS₂）的室中暴露于 CS₁（第二级条件反射阶段）。然后测试对 CS₂的偏好。与对照组相比，接受 CS₁-乙醇配对的青少年对 CS₂表现出更大的偏好，表明乙醇介导的强化，但只有在未用纳洛酮预处理时才表现出这种偏好。纳洛酮对条件反射期间的血液酒精水平没有影响。实验 2表明，乙醇给药后不久引起的运动激活，纳洛酮剂量依赖性地抑制了这种刺激作用。本研究表明，青少年大鼠对乙醇的强化和运动刺激作用敏感。乙醇的这两种作用似乎都由内源性阿片系统激活介导。
