Title |
Possible role of the dopamine D1 receptor in the sensorimotor gating deficits induced by high-fat diet
|
---|---|
Published in |
Psychopharmacology, September 2015
|
DOI | 10.1007/s00213-015-4068-x |
Pubmed ID | |
Authors |
Chisato Wakabayashi, Tadahiro Numakawa, Yoshiko Ooshima, Kotaro Hattori, Hiroshi Kunugi |
Abstract |
High-fat diet (HFD) has been recently reported to induce sensorimotor gating deficits, but the underlying mechanisms are not well understood. 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. 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. 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. 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. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 27 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 10 | 37% |
Researcher | 5 | 19% |
Student > Postgraduate | 2 | 7% |
Student > Bachelor | 2 | 7% |
Other | 1 | 4% |
Other | 2 | 7% |
Unknown | 5 | 19% |
Readers by discipline | Count | As % |
---|---|---|
Neuroscience | 6 | 22% |
Psychology | 5 | 19% |
Agricultural and Biological Sciences | 3 | 11% |
Medicine and Dentistry | 2 | 7% |
Energy | 1 | 4% |
Other | 2 | 7% |
Unknown | 8 | 30% |