RRC ID 36000
Author Wakabayashi C, Numakawa T, Ooshima Y, Hattori K, Kunugi H.
Title Possible role of the dopamine D1 receptor in the sensorimotor gating deficits induced by high-fat diet.
Journal Psychopharmacology (Berl)
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.
Volume 232(24)
Pages 4393-400
Published 2015-12-1
DOI 10.1007/s00213-015-4068-x
PII 10.1007/s00213-015-4068-x
PMID 26359228
MeSH 3,4-Dihydroxyphenylacetic Acid / metabolism Animals Benzazepines / pharmacology Diet, High-Fat* Dopamine / metabolism Dopamine Antagonists / pharmacology* Homovanillic Acid / metabolism Male Mice Mice, Inbred C57BL Mice, Knockout Prefrontal Cortex / drug effects Prefrontal Cortex / metabolism* Prepulse Inhibition / drug effects Prepulse Inhibition / physiology Receptors, Dopamine D1 / antagonists & inhibitors Receptors, Dopamine D1 / metabolism* Receptors, Dopamine D2 / genetics Receptors, Dopamine D2 / metabolism Reflex, Startle / drug effects* Reflex, Startle / physiology Sensory Gating / drug effects* Sensory Gating / physiology
IF 3.13
Times Cited 13
Mice RBRC01081