Instituto de Investigación Médica M. y M. Ferreyra (INIMEC-CONICET), 5016 Córdoba, Argentina.
Behav Brain Res. 2012 Oct 1;234(2):267-77. doi: 10.1016/j.bbr.2012.07.002. Epub 2012 Jul 10.
We recently observed that naloxone, a non-specific opioid antagonist, attenuated operant responding to ethanol in infant rats. Through the use of an operant conditioning technique, we aimed to analyze the specific participation of mu, delta, and kappa opioid receptors on ethanol reinforcement during the second postnatal week. In Experiment 1, infant rats (PDs 14-17) were trained to obtain 5, 7.5, 10, or 15% ethanol, by operant nose-poking. Experiment 2 tested blood ethanol levels (BELs) attained by operant behavior. In Experiment 3, at PDs 16-18, rats received CTOP (mu antagonist: 0.1 or 1.0 mg/kg), naltrindole (delta antagonist: 1.0 or 5.0 mg/kg) or saline before training. In Experiment 4, rats received nor-binaltorphimine (kappa antagonist: 10.0 or 30.0 mg/kg, a single injection after completion of PD 15 operant training), spiradoline mesylate (kappa agonist: 1.0 or 5.0 mg/kg; at PDs 16-18) or saline (PDs 16-18), before the conditioning. Experiments 5 and 6 assessed possible side effects of opioid drugs in locomotor activity (LA) and conditioned taste aversion (CTA). Ethanol at 7.5 and 10% promoted the highest levels of operant responding. BELs were 12-15 mg/dl. In Experiment 3 naltrindole (dose-response effect) and CTOP (the lowest dose) were effective in decreasing operant responding. Nor-binaltorphimine at 10.0 mg/kg and spiradoline at 5.0 mg/kg also blocked ethanol responding. The effects of opioid drugs on ethanol reinforcement cannot be explained by effects on LA or CTA. Even though particular aspects of each opioid receptor require further testing, a fully functional opioid system seems to be necessary for ethanol reinforcement, during early ontogeny.
我们最近观察到，纳洛酮，一种非特异性阿片拮抗剂，可减弱婴儿期大鼠对乙醇的操作性反应。通过使用操作性条件反射技术，我们旨在分析在第二产后周内，μ、δ 和 κ 阿片受体对乙醇强化的特定参与。在实验 1 中，婴儿大鼠（PDs 14-17）通过操作性鼻戳训练获得 5%、7.5%、10%或 15%的乙醇。实验 2 测试了通过操作性行为获得的血液乙醇水平（BELs）。在实验 3 中，在 PDs 16-18 时，大鼠接受 CTOP（μ拮抗剂：0.1 或 1.0mg/kg）、naltrindole（δ 拮抗剂：1.0 或 5.0mg/kg）或生理盐水，然后进行训练。在实验 4 中，大鼠在 PD 15 操作性训练完成后单次注射 nor-binaltorphimine（κ 拮抗剂：10.0 或 30.0mg/kg）、spiradoline 甲磺酸盐（κ 激动剂：1.0 或 5.0mg/kg；PDs 16-18）或生理盐水（PDs 16-18），然后进行条件化。实验 5 和 6 评估了阿片类药物在运动活性（LA）和条件性味觉厌恶（CTA）中的潜在副作用。7.5%和 10%的乙醇促进了最高水平的操作性反应。BELs 为 12-15mg/dl。在实验 3 中，naltrindole（剂量反应效应）和 CTOP（最低剂量）有效降低了操作性反应。nor-binaltorphimine 10.0mg/kg 和 spiradoline 5.0mg/kg 也阻断了乙醇反应。阿片类药物对乙醇强化的作用不能用对 LA 或 CTA 的作用来解释。尽管每个阿片受体的特定方面需要进一步测试，但在早期发育过程中，一个功能齐全的阿片系统似乎是乙醇强化所必需的。
