Separation of the convulsions and antidepressant-like effects produced by the delta-opioid agonist SNC80 in rats
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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.
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.
Slowing the rate of SNC80 administration minimized delta agonist-induced convulsions without altering the effects of SNC80 in the forced swim test.
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.
KeywordsDelta-opioid receptor Antidepressants Convulsions Forced swim test Rats SNC80 Infusion rate
This work was supported by grants from the US Public Health Service Grants DA00254, T32 GM07767, and T32 DA07267.
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