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Effects of pramipexole on the duration of immobility during the forced swim test in normal and ACTH-treated rats

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Abstract

The dopamine D2/D3 receptor agonist pramipexole has clinically been proven to improve depression or treatment-resistant depression. However, the involvement of the dopamine receptor system on the effect of pramipexole on depression remains unclear. We examined the influence of pramipexole on the duration of immobility during the forced swim test in normal and adrenocorticotropic hormone (ACTH)-treated rats and further analyzed the possible role of dopamine receptors in this effect. Additionally, the mechanism by which pramipexole acts in this model was explored specifically in relation to the site of action through the use of microinjections into the intramedial prefrontal cortex and nucleus accumbens. Pramipexole (0.3–1 mg/kg) significantly decreased the duration of immobility in normal and ACTH-treated rats. This effect was blocked by L-741,626, a D2 receptor antagonist, and nafadotride, a D3 receptor antagonist, in normal rats. Furthermore, infusions of pramipexole into the intranucleus accumbens, but not the medial prefrontal cortex, decreased the immobility of normal and ACTH-treated rats during the forced swim test. Taken together, the results of these experiments suggested that pramipexole, administered into the intranucleus accumbens rather than the medial prefrontal cortex, exerted an antidepressant-like effect on ACTH-treated rats via the dopaminergic system. The immobility-decreasing effect of pramipexole may be mediated by dopamine D2 and D3 receptors.

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Acknowledgment

This study was supported in part by a grant-in-aid for scientific research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (No. 19590535).

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Authors and Affiliations

  1. Department of Pharmaceutical Care and Health Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, Okayama, 700-8530, Japan

    Kouhei Kitagawa, Yoshihisa Kitamura, Junya Miyaoka & Toshiaki Sendo

  2. Department of Pharmacy, Okayama University Hospital, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan

    Kouhei Kitagawa & Toshiaki Miyazaki

  3. Department of Clinical Pharmaceutical Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 111 Tsushima-naka, Okayama, 7008530, Japan

    Hiromu Kawasaki

  4. Department of Brain Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan

    Masato Asanuma

  5. Shujitsu University School of Pharmacy, 1-6-1 Nishigawara, Okayama, 703-8516, Japan

    Yutaka Gomita

Authors
  1. Kouhei Kitagawa
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  2. Yoshihisa Kitamura
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  3. Toshiaki Miyazaki
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  4. Junya Miyaoka
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  5. Hiromu Kawasaki
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  6. Masato Asanuma
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  7. Toshiaki Sendo
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  8. Yutaka Gomita
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Correspondence to Yoshihisa Kitamura.

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Kitagawa, K., Kitamura, Y., Miyazaki, T. et al. Effects of pramipexole on the duration of immobility during the forced swim test in normal and ACTH-treated rats. Naunyn-Schmied Arch Pharmacol 380, 59–66 (2009). https://doi.org/10.1007/s00210-009-0405-0

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  • DOI: https://doi.org/10.1007/s00210-009-0405-0

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