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

Eur J Pharmacol. 2009 Feb 14;604(1-3):58-65. doi: 10.1016/j.ejphar.2008.12.021. Epub 2008 Dec 24.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Benzamides / adverse effects*
  • Benzamides / pharmacology
  • Brain / drug effects*
  • Brain / metabolism
  • Electric Stimulation
  • Opioid-Related Disorders / etiology*
  • Piperazines / adverse effects*
  • Piperazines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Opioid, delta / agonists*
  • Seizures / chemically induced
  • Self Stimulation / drug effects*


  • Benzamides
  • Piperazines
  • Receptors, Opioid, delta
  • 4-(alpha-(4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N,N-diethylbenzamide