The selective non-peptidic delta opioid agonist SNC80 does not facilitate intracranial self-stimulation in rats.
The selective non-peptidic delta opioid agonist SNC80 does not facilitate intracranial self-stimulation in rats.
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DOI：
10.1016/j.ejphar.2008.12.021
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发表时间：
2009-02-14
影响因子：
5
通讯作者：
Negus SS
中科院分区：
文献类型：
--
作者：
Do Carmo GP;Folk JE;Rice KC;Chartoff E;Carlezon WA Jr;Negus SS
δ阿片受体激动剂正在开发用于各种临床应用，大鼠中的一些发现提高了具有这种机制的药物具有滥用倾向的可能性。本研究评估了非肽类δ阿片受体激动剂SNC 80在大鼠颅内自我刺激（ICSS）试验中的作用。在多个刺激频率下检查ICSS，以允许生成频率响应率曲线并评价实验操作产生的曲线偏移。药物引起的ICSS频率-频率曲线的偏移通常被解释为滥用倾向的证据。然而，SNC 80（1.0-10 mg/kg s.c.; 10-56 mg/kg i.p.）在本研究中产生惊厥的剂量或既往研究中产生其他效应（如抗抑郁作用）的剂量下，未能改变ICSS频率-速率曲线。为了比较，单胺麻醉剂d-苯丙胺（0.1- 1.0mg/kg，i. p.）和κ激动剂U69，593（0.1- 0.56mg/kg，i. p.）分别在ICSS频率-速率曲线中产生剂量依赖性的Δ T和Δ T偏移，证实了该程序对药物作用的敏感性。ICSS频率-速率曲线也通过两种非药物操作（刺激强度降低和反应要求增加）发生偏移。因此，SNC 80未能促进或减弱ICSS维持的反应条件下，其他药理学和非药理学操作是有效的。这些结果表明，非肽类δ阿片受体激动剂在大鼠中具有可忽略的滥用相关效应。
Delta opioid receptor agonists are under development for a variety of clinical applications, and some findings in rats raise the possibility that agents with this mechanism have abuse liability. The present study assessed the effects of the non-peptidic delta opioid agonist SNC80 in an assay of intracranial self-stimulation (ICSS) in rats. ICSS was examined at multiple stimulation frequencies to permit generation of frequency-response rate curves and evaluation of curve shifts produced by experimental manipulations. Drug-induced leftward shifts in ICSS frequency-rate curves are often interpreted as evidence of abuse liability. However, SNC80 (1.0-10 mg/kg s.c.; 10-56 mg/kg i.p.) failed to alter ICSS frequency-rate curves at doses up to those that produced convulsions in the present study or other effects (e.g. antidepressant effects) in previous studies. For comparison, the monoamine releaser d-amphetamine (0.1-1.0 mg/kg, i.p.) and the kappa agonist U69,593 (0.1-0.56 mg/kg, i.p.) produced dose-dependent leftward and rightward shifts, respectively, in ICSS frequency-rate curves, confirming the sensitivity of the procedure to drug effects. ICSS frequency-rate curves were also shifted by two non-pharmacological manipulations (reductions in stimulus intensity and increases in response requirement). Thus, SNC80 failed to facilitate or attenuate ICSS-maintained responding under conditions in which other pharmacological and non-pharmacological manipulations were effective. These results suggest that non-peptidic delta opioid receptor agonists have negligible abuse-related effects in rats.
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影响因子：
4.7
作者：
Duvauchelle, CL;Fleming, SM;Kornetsky, C
通讯作者：
Kornetsky, C
影响因子：
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作者：
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作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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