Separation of the convulsions and antidepressant-like effects produced by the delta-opioid agonist SNC80 in rats.

Abstract

RATIONALE:

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.

MATERIALS AND 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.

• Authors: Emily M Jutkiewicz, Kenner C Rice, John R Traynor, James H Woods
• Journal: Psychopharmacology (Psychopharmacology (Berl)) Vol. 182 Issue 4 Pg. 588-96 (Nov 2005) ISSN: 0033-3158 [Print] Germany
• PMID: 16163520 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antidepressive Agents
• Benzamides
• NTI compound
• Piperazines
• Receptors, Opioid, delta
• Tritium
• 4-(alpha-(4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N,N-diethylbenzamide
• Naltrexone

Topics

• Analysis of Variance
• Animals
• Antidepressive Agents (administration & dosage, adverse effects)
• Behavior, Animal (drug effects)
• Benzamides (administration & dosage, adverse effects)
• Dose-Response Relationship, Drug
• Drug Administration Routes
• Drug Interactions
• Male
• Naltrexone (analogs & derivatives, pharmacokinetics)
• Piperazines (administration & dosage, adverse effects)
• Rats
• Rats, Sprague-Dawley
• Receptors, Opioid, delta (antagonists & inhibitors)
• Restraint, Physical
• Seizures (etiology)
• Swimming
• Time Factors
• Tritium (pharmacokinetics)