Ramelteon Improves Post-traumatic Stress Disorder-Like Behaviors Exhibited by Fatty Acid-Binding Protein 3 Null Mice

Molecular Neurobiology
Yasushi YabukiKohji Fukunaga

Abstract

We previously reported that fatty acid-binding protein 3 (FABP3) knockout (Fabp3 -/-) mice exhibit abnormal dopamine-related behaviors such as enhanced dopamine D2 receptor antagonist-induced catalepsy behaviors. Here, we report that Fabp3 null mice exhibit cognitive deficits, hyperlocomotion and impaired fear extinction, and thus show post-traumatic stress disorder (PTSD)-like behaviors. Notably, chronic administration of ramelteon (1.0 mg/kg, p.o.), a melatonin receptor agonist, improved all PTSD-like behaviors tested in Fabp3 -/- mice. Relevant to mechanisms underlying impaired fear extinction, we observed significantly reduced levels of Ca2+/calmodulin-dependent protein kinase II (CaMKII) autophosphorylation without changes in ERK phosphorylation in the anterior cingulate cortex (ACC). Inversely, CaMKII autophosphorylation increased in the basolateral amygdala (BLA) but remained relatively unchanged in hippocampus of Fabp3 -/- mice. Likewise, the number of c-Fos-positive neurons in BLA significantly increased after exposure to contextual fear conditions but remained unchanged in the central nucleus of the amygdala (CeA). Importantly, chronic ramelteon administration (1.0 mg/kg, p.o.) restored abnormal c-Fos expression and C...Continue Reading

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Citations

Sep 11, 2019·Current Opinion in Clinical Nutrition and Metabolic Care·Heli XuJudith Storch
Jul 28, 2019·International Journal of Molecular Sciences·Yasushi Yabuki, Kohji Fukunaga
May 28, 2019·Molecular Neurobiology·Gofarana WilarKohji Fukunaga
Oct 10, 2018·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Kohji FukunagaKazuya Matsuo
Mar 27, 2020·International Journal of Molecular Sciences·Yasushi YabukiKohji Fukunaga
Aug 6, 2020·International Journal of Molecular Sciences·Yasushi YabukiKohji Fukunaga
Jan 7, 2021·International Journal of Molecular Sciences·Kazuya MatsuoKohji Fukunaga
Feb 20, 2021·Anatomical Science International·Yui Yamamoto, Yuji Owada

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