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Alterations in behavioral responses to dopamine agonists in olfactory bulbectomized mice: relationship to changes in the striatal dopaminergic system

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Abstract

Background

Olfactory bulbectomy (OBX) in rodents is considered a putative animal model of depression. It has been reported that some abnormal behaviors observed in this animal model of depression involve dopaminergic neurons of the mesolimbic pathway. Therefore, we examined changes in the dopaminergic system in the caudate putamen (CPu), nucleus accumbens core (NAcC), and shell (NAcSh) of OBX mice and whether or not these alterations were reversed by chronic administration of imipramine.

Methods

We observed climbing behavior, which is a dopamine (DA) receptor-associated behavior, to demonstrate changes in the dopaminergic system of the mesolimbic pathway, when mice were administrated either the nonselective DA agonist apomorphine only or were pre-treated with the selective D1 antagonist SCH23390, with the selective D2 antagonist sulpiride, or with the D2/D3 partial agonist aripiprazole (ARI). Moreover, we examined tyrosine hydroxylase (TH) and D1- and D2-like receptor levels in the CPu, NAcC, and NAcSh using immunohistochemistry and autoradiography.

Results

The OBX group exhibited significantly enhanced apomorphine-induced climbing behavior, and this enhanced behavior was reversed by administration of sulpiride, ARI, and imipramine but not SCH23390. Moreover, we found a reduction in TH levels in the CPu, NAcC, and NAcSh of OBX mice and an increase in D2 receptor densities in the NAcC of OBX mice. The increased D2 receptor density observed in OBX mice was reversed by imipramine administration.

Conclusions

These findings reveal that OBX mice display enhanced DA receptor responsiveness, which may relate to some of the behavioral abnormalities reported in this animal model.

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Acknowledgments

This study was supported in part by Grants-in-Aid for Scientific Research (26460102) and Matching Fund Subsidy for Private Universities from the Ministry of Education, Culture, Sports, Science, and Technology of Japan. The authors would like to thank Ms. Reina Hoshi, Mr. Shusuke Kawamura, Ms. Jia-Rong Lin, Ms. Eri Kikuchi, and Ms. Wakana Sakuma of Tohoku Pharmaceutical University for their technical assistance.

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Authors and Affiliations

  1. Department of Pharmacology, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai, 981-8558, Japan

    Kohei Takahashi, Osamu Nakagawasai, Wataru Nemoto, Takeharu Nakajima & Koichi Tan-No

  2. Department of Health Science, Ariake University of Medical and Health Science, 2-9-1 Ariake, Koto-Ku, Tokyo, 135-0063, Japan

    Yuichiro Arai

  3. Department of Physiology, School of Medicine, Showa University, 1-5-8 Hatanodai, Shinagawa-Ku, Tokyo, 142-8666, Japan

    Tadashi Hisamitsu

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  1. Kohei Takahashi
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  2. Osamu Nakagawasai
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  3. Wataru Nemoto
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  4. Takeharu Nakajima
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  5. Yuichiro Arai
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  7. Koichi Tan-No
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Correspondence to Osamu Nakagawasai.

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All experiments were performed with the approval of the Ethics Committee for Animal Experimentation at Tohoku Pharmaceutical University and according to the National Institutes of Health Guide for the Care and Use of Laboratory Animals.

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Takahashi, K., Nakagawasai, O., Nemoto, W. et al. Alterations in behavioral responses to dopamine agonists in olfactory bulbectomized mice: relationship to changes in the striatal dopaminergic system. Psychopharmacology 233, 1311–1322 (2016). https://doi.org/10.1007/s00213-016-4224-y

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  • DOI: https://doi.org/10.1007/s00213-016-4224-y

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