The selective non-peptidic delta opioid agonist SNC80 does not facilitate intracranial self-stimulation in rats.
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.
Do Carmo
Gail Pereira
GP
Alcohol and Drug Abuse Research Center, McLean Hospital-Harvard Medical School, Belmont, MA 02478, United States.
Folk
John E
JE
Rice
Kenner C
KC
Chartoff
Elena
E
Carlezon
William A
WA
Negus
S Stevens
SS
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001549:Benzamides / Q000009:adverse effects* / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004558:Electric Stimulation; D009293:Opioid-Related Disorders / Q000209:etiology*; D010879:Piperazines / Q000009:adverse effects* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000819:agonists*; D012640:Seizures / Q000139:chemically induced; D012653:Self Stimulation / Q000187:drug effects*
D001549:Benzamides; D010879:Piperazines; D017465:Receptors, Opioid, delta; C088464:4-(alpha-(4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N,N-diethylbenzamide