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Volume 23
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10.3390/ijms23137436
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Article

Therapeutic Effects of Quetiapine and 5-HT1A Receptor Agonism on Hyperactivity in Dopamine-Deficient Mice

by
Yukiko Ochiai
1,2,
Masayo Fujita
1,
Yoko Hagino
1,
Kazuto Kobayashi
3,
Ryoichi Okiyama
2,
Kazushi Takahashi
2 and
Kazutaka Ikeda
1,*
1
Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan
2
Department of Neurology, Tokyo Metropolitan Neurological Hospital, Tokyo 183-0042, Japan
3
Department of Molecular Genetics, Institute of Biomedical Sciences, Fukushima Medical University, Fukushima 960-1295, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2022, 23(13), 7436; https://doi.org/10.3390/ijms23137436
Submission received: 9 June 2022 / Revised: 30 June 2022 / Accepted: 30 June 2022 / Published: 4 July 2022
(This article belongs to the Special Issue Transgenic Mice in Human Diseases: Insights from Molecular Research 3.0)
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Abstract

Some diseases that are associated with dopamine deficiency are accompanied by psychiatric symptoms, including Parkinson’s disease. However, the mechanism by which this occurs has not been clarified. Previous studies found that dopamine-deficient (DD) mice exhibited hyperactivity in a novel environment. This hyperactivity is improved by clozapine and donepezil, which are used to treat psychiatric symptoms associated with dopamine deficiency (PSDD). We considered that DD mice could be used to study PSDD. In the present study, we sought to identify the pharmacological mechanism of PSDD. We conducted locomotor activity tests by administering quetiapine and drugs that have specific actions on serotonin (5-hydroxytryptamine [5-HT]) receptors and muscarinic receptors. Changes in neuronal activity that were induced by drug administration in DD mice were evaluated by examining Fos immunoreactivity. Quetiapine suppressed hyperactivity in DD mice while the 5-HT1A receptor antagonist WAY100635 inhibited this effect. The number of Fos-positive neurons in the median raphe nucleus increased in DD mice that exhibited hyperactivity and was decreased by treatment with quetiapine and 5-HT1A receptor agonists. In conclusion, hyperactivity in DD mice was ameliorated by quetiapine, likely through 5-HT1A receptor activation. These findings suggest that 5-HT1A receptors may play a role in PSDD, and 5-HT1A receptor-targeting drugs may help improve PSDD.
Keywords: psychiatric symptoms; dopamine deficiency; dopamine-deficient mice; 5-HT1A receptor; Parkinson’s disease psychiatric symptoms; dopamine deficiency; dopamine-deficient mice; 5-HT1A receptor; Parkinson’s disease

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MDPI and ACS Style

Ochiai, Y.; Fujita, M.; Hagino, Y.; Kobayashi, K.; Okiyama, R.; Takahashi, K.; Ikeda, K. Therapeutic Effects of Quetiapine and 5-HT1A Receptor Agonism on Hyperactivity in Dopamine-Deficient Mice. Int. J. Mol. Sci. 2022, 23, 7436. https://doi.org/10.3390/ijms23137436

AMA Style

Ochiai Y, Fujita M, Hagino Y, Kobayashi K, Okiyama R, Takahashi K, Ikeda K. Therapeutic Effects of Quetiapine and 5-HT1A Receptor Agonism on Hyperactivity in Dopamine-Deficient Mice. International Journal of Molecular Sciences. 2022; 23(13):7436. https://doi.org/10.3390/ijms23137436

Chicago/Turabian Style

Ochiai, Yukiko, Masayo Fujita, Yoko Hagino, Kazuto Kobayashi, Ryoichi Okiyama, Kazushi Takahashi, and Kazutaka Ikeda. 2022. "Therapeutic Effects of Quetiapine and 5-HT1A Receptor Agonism on Hyperactivity in Dopamine-Deficient Mice" International Journal of Molecular Sciences 23, no. 13: 7436. https://doi.org/10.3390/ijms23137436

APA Style

Ochiai, Y., Fujita, M., Hagino, Y., Kobayashi, K., Okiyama, R., Takahashi, K., & Ikeda, K. (2022). Therapeutic Effects of Quetiapine and 5-HT1A Receptor Agonism on Hyperactivity in Dopamine-Deficient Mice. International Journal of Molecular Sciences, 23(13), 7436. https://doi.org/10.3390/ijms23137436

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