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Possible role of the dopamine D1 receptor in the sensorimotor gating deficits induced by high-fat diet

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Abstract

Rationale

High-fat diet (HFD) has been recently reported to induce sensorimotor gating deficits, but the underlying mechanisms are not well understood.

Objective

The purpose of this study is to determine whether HFD induces long-lasting deficits in sensorimotor gating and to examine the involvement of altered dopamine (DA) function.

Methods

C57BL/6J mice were fed HFD for 10 weeks and then normal diet (ND) for 4 weeks. DA D2 receptor (D2R) knockout (KO) mice were also fed HFD for 10 weeks. The mice were evaluated for prepulse inhibition (PPI) of acoustic startle after HFD and the subsequent 4-week ND. We evaluated the effect of SCH23390, a D1 receptor (D1R) antagonist, on PPI and measured protein expression levels of D1R and D2R in the prefrontal cortex (PFC) in HFD mice. The concentrations of monoamines and their metabolites in the cortices of 10-week HFD or ND mice were measured using high performance liquid chromatography.

Results

Long-term HFD-induced PPI disruption in WT and D2R KO mice. Even after 4 weeks of subsequent ND, PPI remained to be disrupted. SCH23390 mitigated the PPI disruption. In HFD animals, D1R protein expression in the PFC was significantly decreased, while DA, homovanillic acid, and 3,4-dihydroxyphenylacetic acid levels in the cortex were increased.

Conclusion

This is the first evidence that HFD can induce long-lasting deficits in sensorimotor gating through alteration of cortical levels of DA and its metabolites. Our data suggest that HFD-induced PPI deficits are related to altered D1R signaling and that D1R antagonists may have therapeutic effects on the deficits.

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Acknowledgments

This study was supported by the Intramural Research Grant for Neurological and Psychiatric Disorders of NCNP, Health and Labour Sciences Research Grants, and the Strategic Research Program for Brain Sciences by the Ministry of Education, Culture, Sports, Science and Technology of Japan. We thank Mr. K. Yamamoto for technical assistance.

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Authors and Affiliations

  1. Department of Mental Disorder Research, National Center of Neurology and Psychiatry, National Institute of Neuroscience, 4-1-1, Ogawa-higashi, Kodaira, Tokyo, 187-8502, Japan

    Chisato Wakabayashi, Tadahiro Numakawa, Yoshiko Ooshima, Kotaro Hattori & Hiroshi Kunugi

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  1. Chisato Wakabayashi
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  2. Tadahiro Numakawa
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  3. Yoshiko Ooshima
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  4. Kotaro Hattori
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  5. Hiroshi Kunugi
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Correspondence to Hiroshi Kunugi.

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Wakabayashi, C., Numakawa, T., Ooshima, Y. et al. Possible role of the dopamine D1 receptor in the sensorimotor gating deficits induced by high-fat diet. Psychopharmacology 232, 4393–4400 (2015). https://doi.org/10.1007/s00213-015-4068-x

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  • DOI: https://doi.org/10.1007/s00213-015-4068-x

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