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

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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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Acknowledgements

This work was supported by grants from the US Public Health Service Grants DA00254, T32 GM07767, and T32 DA07267.

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Authors and Affiliations

  1. Department of Pharmacology, University of Michigan Medical School, 1301 MSRB III, Ann Arbor, MI, 48109-0632, USA

    Emily M. Jutkiewicz, John R. Traynor & James H. Woods

  2. NIH, Rm. B1-23, Bldg. 8, MSC 0815, Bethesda, MD, 20892, USA

    Kenner C. Rice

Authors
  1. Emily M. Jutkiewicz
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  2. Kenner C. Rice
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  3. John R. Traynor
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  4. James H. Woods
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Correspondence to Emily M. Jutkiewicz.

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Jutkiewicz, E.M., Rice, K.C., Traynor, J.R. et al. Separation of the convulsions and antidepressant-like effects produced by the delta-opioid agonist SNC80 in rats. Psychopharmacology 182, 588–596 (2005). https://doi.org/10.1007/s00213-005-0138-9

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  • DOI: https://doi.org/10.1007/s00213-005-0138-9

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