The selective non-peptidic delta opioid agonist SNC80 does not facilitate intracranial self-stimulation in rats

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• 作者：Gail Pereira Do Carmo ; John E. Folk ; Kenner C. Rice ; Elena Chartoff ; William A. Carlezon Jr. ; S. Stevens Negus
• 关键词：Delta opioid receptor agonists ; SNC80 ; Amphetamine ; U69 ; 593 ; Intracranial self-stimulation
• 刊名：European Journal of Pharmacology
• 出版年：2009
• 出版时间：14 February 2009
• 年：2009
• 卷：604
• 期：1-3
• 页码：58-65
• 全文大小：747 K

文摘

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.