纳洛酮诱导的阿片类药物初治 Lewis 和 Fischer 344 大鼠的味觉厌恶。
Naloxone-induced taste aversions in opiate-naïve Lewis and Fischer 344 rat strains.
机构信息
Psychopharmacology Laboratory, Department of Psychology, American University, 4400 Massachusetts Avenue NW, Washington, DC 20016, United States.
出版信息
Drug Alcohol Depend. 2012 Apr 1;122(1-2):152-5. doi: 10.1016/j.drugalcdep.2011.09.016. Epub 2011 Oct 11.
BACKGROUND
The Lewis (LEW) and Fischer (F344) rat strains appear differentially sensitive to the aversive effects of several used and abused drugs. Naloxone, a mu opioid receptor antagonist that induces aversions in outbred rats but has no abuse potential, was assessed to determine the characteristics of compounds for which the strains differ.
METHODS
Opioid-naïve male LEW and F344 rats were given access to saccharin followed by low (Experiment 1) and high (Experiment 2) doses of naloxone every 4th day for five pairings. Aversions were assessed in both one-bottle and two-bottle tests.
RESULTS
In Experiment 1, aversions were evident at 10mg/kg (one-bottle) and at 5.6 and 10mg/kg (two-bottle) with no apparent strain difference for either assessment. In Experiment 2, aversions were evident for LEW animals (but not F344) at 18 and 32 mg/kg (one-bottle). LEW animals injected with 32 mg/kg displayed greater aversions than F344 animals receiving the same dose. Both strains displayed aversions at all doses in the two-bottle test with no strain difference.
CONCLUSIONS
Naloxone induced aversions that were strain dependent only at specific doses and under the one-bottle testing condition. These results parallel those of several other used and abused drugs but differ dramatically from those seen with morphine in the two strains (F344>LEW). Further assessments utilizing the LEW-F344 model should investigate other drugs to establish the set of compounds for which the strains differ and to characterize the mechanism underlying the observed differences.
背景
LEW（刘易斯）和 Fischer（F344）大鼠品系对几种已使用和滥用药物的厌恶效应表现出不同的敏感性。纳洛酮是一种μ阿片受体拮抗剂，在杂交大鼠中会引起厌恶反应，但没有滥用潜力，本研究评估了该化合物的特征，以确定不同品系之间的差异。
方法
给予未接受过阿片类药物的雄性 LEW 和 F344 大鼠蔗糖，然后每隔 4 天给予低（实验 1）和高（实验 2）剂量的纳洛酮，共进行五次配对。在单瓶和双瓶测试中评估厌恶反应。
结果
在实验 1 中，10mg/kg（单瓶）和 5.6mg/kg 和 10mg/kg（双瓶）时出现了明显的厌恶反应，两种评估方法均未显示出明显的品系差异。在实验 2 中，18mg/kg 和 32mg/kg（单瓶）时 LEW 动物出现了厌恶反应（但 F344 动物没有）。接受 32mg/kg 纳洛酮注射的 LEW 动物比接受相同剂量的 F344 动物表现出更大的厌恶反应。两种品系在双瓶测试中均在所有剂量下表现出厌恶反应，且无品系差异。
结论
纳洛酮诱导的厌恶反应仅在特定剂量和单瓶测试条件下依赖于品系。这些结果与其他几种已使用和滥用药物的结果相似，但与两种品系（F344>LEW）中吗啡的结果截然不同。利用 LEW-F344 模型进行的进一步评估应研究其他药物，以确定品系之间存在差异的化合物，并对观察到的差异的机制进行表征。
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