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Role of δ-opioid receptor subtypes in anxiety-related behaviors in the elevated plus-maze in rats

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Abstract

Rationale

Recent studies have shown that endogenous opioid systems are associated with the regulation of emotional responses. In particular, it has been reported that δ-opioid receptors act naturally to inhibit stress and anxiety.

Objective

The present study was designed to examine the possible involvement of opioid δ-receptor subtypes in the anxiety-related behavior in the elevated-plus-maze test.

Methods

Six-week-old male Lewis rats were used. The total numbers of visits to the closed and open arms and the cumulative time spent and visits in the open arms were determined. Plasma corticosterone levels were measured by enzyme immunoassay.

Results

Naltrindole (NTI), a δ-opioid receptor antagonist (3 mg/kg s.c.), induced a significant decrease in the percentages of time spent and visits in the open arms. Naltriben (NTB), a δ2-opioid receptor antagonist (3 mg/kg s.c.), but not 7-benzylidenenaltrexone, a δ1-opioid receptor antagonist, produced similar anxiety-related behaviors in the elevated plus-maze. These effects of NTI and NTB were antagonized by pretreatment with (+)-4-[(aR)-a-((2S,5R)-4-allyl-2,5-dimethyl-1piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (SNC80), a δ-opioid receptor agonist. Furthermore, after exposure to the elevated plus-maze, the maximal increase in the plasma corticosterone level in NTI-treated rats was clearly higher than that in vehicle-treated rats. However, when NTI and SNC80 were coadministered, higher levels of plasma corticosterone were not seen after exposure to the elevated plus-maze.

Conclusion

These results suggest that endogenous δ2-opioid-receptor-mediated systems are involved in the regulation of anxiety-related behaviors and might play a physiologically important role in the regulation of adrenocortical activity.

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Acknowledgements

We thank Ms. M. Ishihara, Mr. M. Ishikawa, Ms. C. Nozaki, Mr. N. Hirose, and Ms. A Tuyuki for their excellent technical assistance. We would also like to thank Drs. K. Kawai and T. Suzuki (Toray Industries, Inc.,) for their constant support.

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Authors and Affiliations

  1. Department of Pathophysiology & Therapeutics, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 4-41, Ebara 2-chome, Shinagawa-ku, Tokyo, 142-8501, Japan

    Akiyoshi Saitoh, Yuji Yoshikawa, Kenji Onodera & Junzo Kamei

  2. Department of Dental Pharmacology, Okayama University Graduate School of Medicine and Dentistry, Okayama, 700-8525, Japan

    Kenji Onodera

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  1. Akiyoshi Saitoh
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  2. Yuji Yoshikawa
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  3. Kenji Onodera
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  4. Junzo Kamei
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Correspondence to Junzo Kamei.

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Saitoh, A., Yoshikawa, Y., Onodera, K. et al. Role of δ-opioid receptor subtypes in anxiety-related behaviors in the elevated plus-maze in rats. Psychopharmacology 182, 327–334 (2005). https://doi.org/10.1007/s00213-005-0112-6

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  • DOI: https://doi.org/10.1007/s00213-005-0112-6

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