Journal
PSYCHOPHARMACOLOGY
Volume 182, Issue 4, Pages 588-596Publisher
SPRINGER
DOI: 10.1007/s00213-005-0138-9
Keywords
delta-opioid receptor; antidepressants; convulsions; forced swim test; rats; SNC80; infusion rate
Categories
Funding
- NIDA NIH HHS [DA00254, T32 DA007267, P01 DA000254, P50 DA000254, T32 DA07267, K21 DA000254] Funding Source: Medline
- NIGMS NIH HHS [T32 GM07767, T32 GM007767] Funding Source: Medline
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Rationale: Delta-opioid agonists produce a number of behavioral effects, including convulsions, anti-nociception, locomotor stimulation, and anti-depressant-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.
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