Effects of yohimbine on the antinociceptive and place conditioning effects of opioid agonists in rodents
Effects of yohimbine on the antinociceptive and place conditioning effects of opioid agonists in rodents
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DOI：
10.1038/sj.bjp.0704057
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发表时间：
2001-05-01
影响因子：
7.3
通讯作者：
Alguacil, LF
中科院分区：
文献类型：
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作者：
Morales, L;Perez-Garcia, C;Alguacil, LF
1.通过作用于异源机制的药物对阿片作用进行药理学调节，可能有助于克服与使用阿片激动剂有关的一些主要问题。在前人关于育亨宾与阿片类药物相互作用的研究基础上，我们进一步研究了育亨宾对吗啡的抗伤害作用和正负强化作用的影响（μ阿片受体偏好激动剂），U-50，488（κ激动剂）和SNC 80（δ激动剂）。2育亨宾预处理完全阻断了小鼠尾中三种阿片激动剂提供的抗伤害感受作用。3在小鼠热板试验中，在相同剂量下，用育亨宾观察到SNC 80和U-50，488诱导的抗伤害感受的类似阻断。在这种范例中，κ激动剂的作用非常轻微，育亨宾的作用相当可变。4在SD（Sprague-Dawley）雄性大鼠的原位条件反射实验中，单独的育亨宾没有活性，但它限制了吗啡和SNC 80诱导的偏好和U-50，488的厌恶作用。育亨宾和U-50，488的组合也观察到新奇偏好受损。5得出的结论是，育亨宾倾向于限制阿片类抗伤害感受和μ和δ阿片类激动剂的成瘾潜力。选择性更强的药物可能有助于了解这些作用的机制。
1 The pharmacological modulation of opioid actions by drugs acting on heterologous mechanisms could be useful to overcome some of the main problems associated with the use of opiate agonists. Based on previous findings on the interactions between yohimbine and opioid drugs, we have further studied the effects of yohimbine on the antinociceptive and positive-negative reinforcing effects of morphine (mu opioid receptor-preferring agonist), U-50,488 (kappa agonist) and SNC80 (delta agonist).2 Pretreatment with yohimbine completely blocked the antinociception provided by the three opioid agonists in the mouse tail-immersion test.3 A similar blockade of SNC80 and U-50,488-induced antinociception was observed with yohimbine in the mouse hot plate test at the same doses. In this paradigm, the effect of the kappa agonist was very slight and the actions of yohimbine rather variable.4 In place conditioning experiments with SD (Sprague-Dawley) male rats, yohimbine alone was inactive but it limited the preference induced by morphine and SNC80 and the aversive effect of U-50,488. Impaired novelty preference was also observed with the combination of yohimbine and U-50,488.5 It is concluded that yohimbine tends to limit opioid antinociception and the addictive potential of mu and delta opioid agonists. More selective drugs could help to understand the mechanisms involved in these actions.