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Comparative Study
.2005 Nov;182(4):588-96.
doi: 10.1007/s00213-005-0138-9. Epub 2005 Oct 19.

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

Affiliations
Comparative Study

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

Emily M Jutkiewicz et al. Psychopharmacology (Berl).2005 Nov.

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.

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Figures

Fig. 1
Fig. 1
The effects of fast 20-s infusion of IV SNC80 on convulsive (a) and antidepressant-like effects in the forced swim test (b) in Sprague–Dawley rats (N=6 per dose). Drug was injected 30 min prior to the forced swim test. Thebars and vertical lines above each bar represent the mean and standard error of the mean (SEM) for immobility (open bars), swimming counts (single-hatched bars), and climbing counts (double-hatched bars). * indicatesp<0.05, and ** indicatesp<0.01, as compared to vehicle as determined by Dunnett’s post hoc test
Fig. 2
Fig. 2
The effects of vehicle, 0.1, 1.0, or 10 mg kg−1 naltrin-dole (NTI) administered (s.c.) 30 min prior to vehicle or various doses of IV SNC80 on convulsive (a) and antidepressant-like effects in the forced swim test (b) in Sprague–Dawley rats (N=6 per condition). Antidepressant-like effects are expressed as mean immobility counts only
Fig. 3
Fig. 3
Comparison of the convulsive (a) and antidepressant-like effects (b) of SNC80 measured following s.c. administration or fast 20-s IV SNC80 infusion (N=6 per dose). Drug was injected 60 min prior to the forced swim test for s.c. administration or 30 min prior to the forced swim test for IV SNC80. Antidepressant-like effects are expressed as mean immobility counts only
Fig. 4
Fig. 4
The effects of IV SNC80 by fast 20-s, slow 20-min, or slow 60-min infusions on convulsions (a) and antidepressant-like effects in the forced swim test (b). Vehicle or a single dose of IV SNC80 was infused over the duration listed above, and rats were exposed to the swim session 30 min after the termination of the infusion. Antidepressant-like effects are expressed as mean immobility counts only
Fig. 5
Fig. 5
The effects of 10 mg kg−1 NTI administered (s.c.) 30 min prior to IV SNC80 by fast 20-s, slow 20-min, or slow 60-min infusions on the convulsive (a) and antidepressant-like effects in the forced swim test (b) in Sprague–Dawley rats (N=6 per condition). Thebars andvertical lines above eachbar represent the mean and standard error of the mean (SEM) for SNC80 alone (open bars), 10 mg kg−1 SNC80 alone (single-hatched bars), or 10 mg kg−1 NTI administered prior to 10 mg kg−1 SNC80 (double-hatched bars). ** indicatesp<0.01 as compared to Ctrl determined by one-way ANOVA with Dunnett’s post hoc test
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