Separation of the convulsions and antidepressant-like effects produced by the delta-opioid agonist SNC80 in rats.
BACKGROUND
Delta-opioid agonists produce a number of behavioral effects, including convulsions, antinociception, locomotor stimulation, and antidepressant-like effects. The development of these compounds as treatments for depression is limited by their convulsive effects. Therefore, determining how to separate the convulsive and antidepressant-like characteristics of these compounds is essential for their potential clinical use.


OBJECTIVE
The present study tests the hypothesis that the rate of delta-opioid agonist administration greatly contributes to the convulsive properties, but not the antidepressant-like effects, of delta-opioid agonists.


METHODS
The delta-opioid agonist SNC80 (1, 3.2, and 10 mg kg-1 or vehicle) was administered to Sprague-Dawley rats by intravenous infusion over different durations of time (20 s, 20, or 60 min). Convulsions were measured by observation prior to determining antidepressant-like effects in the forced swim test.


RESULTS
Slowing the rate of SNC80 administration minimized delta agonist-induced convulsions without altering the effects of SNC80 in the forced swim test.


CONCLUSIONS
These data suggest that delta agonist-induced antidepressant properties are independent of convulsive effects, and that it may be possible to eliminate the convulsions produced by delta agonists, further promoting their potential clinical utility.
Jutkiewicz
Emily M
EM
Department of Pharmacology, University of Michigan Medical School, 1301 MSRB III, Ann Arbor, MI 48109-0632, USA. ejutkiew@umich.edu
Rice
Kenner C
KC
Traynor
John R
JR
Woods
James H
JH
D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001522:Behavior, Animal / Q000187:drug effects; D001549:Benzamides / Q000008:administration & dosage / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004347:Drug Interactions; D008297:Male; D009271:Naltrexone / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors*; D012149:Restraint, Physical; D012640:Seizures / Q000209:etiology*; D013550:Swimming; D013997:Time Factors; D014316:Tritium / Q000493:pharmacokinetics
D000928:Antidepressive Agents; D001549:Benzamides; C114628:NTI compound; D010879:Piperazines; D017465:Receptors, Opioid, delta; D014316:Tritium; C088464:4-(alpha-(4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N,N-diethylbenzamide; D009271:Naltrexone