Abstract |
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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Authors | Gail Pereira Do Carmo, John E Folk, Kenner C Rice, Elena Chartoff, William A Carlezon Jr, S Stevens Negus |
Journal | European journal of pharmacology
(Eur J Pharmacol)
Vol. 604
Issue 1-3
Pg. 58-65
(Feb 14 2009)
ISSN: 1879-0712 [Electronic] Netherlands |
PMID | 19133255
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural)
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Chemical References |
- Benzamides
- Piperazines
- Receptors, Opioid, delta
- 4-(alpha-(4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N,N-diethylbenzamide
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Topics |
- Animals
- Behavior, Animal
(drug effects)
- Benzamides
(adverse effects, pharmacology)
- Brain
(drug effects, metabolism)
- Electric Stimulation
- Opioid-Related Disorders
(etiology)
- Piperazines
(adverse effects, pharmacology)
- Rats
- Rats, Sprague-Dawley
- Receptors, Opioid, delta
(agonists)
- Seizures
(chemically induced)
- Self Stimulation
(drug effects)
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