Involvement of the ventral, but not dorsal, hippocampus in anxiety-like behaviors in mice exposed to the elevated plus maze: participation of CRF1 receptor and PKA pathway

Natalia Bonetti Bertagna, Paulla Giovanna Cabral dos Santos, Rafaella Misael Queiroz, Gustavo Juliate Damaceno Fernandes,Fabio Cardoso Cruz,Tarciso Tadeu Miguel

PHARMACOLOGICAL REPORTS(2020)

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摘要
Background The hippocampus is a limbic structure involved in anxiety-like behaviors. We aimed to evaluate the role of the dorsal (DH) and ventral (VH) hippocampus in anxiety-like behaviors in the elevated plus maze (EPM). Methods We inhibited these brain regions using cobalt chloride (CoCl 2 : 1.0 nmol) microinjections. We also investigated the involvement of corticotropin-releasing factor (CRF) action and protein kinase A (PKA) pathway using intra-DH and intra-VH microinjections of the CRF1 receptor antagonist CP376395 (0, 3.0, or 6.0 nmol) and the PKA inhibitor H-89 (0, 2.5, or 5.0 nmol). Results The results indicated that intra-VH CoCl 2 microinjection increased the percentage of time spent and entries in the open arms. The mice also exhibited fewer stretch attend postures in the protected area and increased percentage of open arm entries. Further, intra-VH injection of 3.0 nmol CP376395 increased time spent in the open arms. Intra-DH injection of 6.0 nmol CP376395 increased the frequency of unprotected head dipping, whereas intra-VH injection of 6 nmol CP376395 increased the frequency of protected head dipping. Intra-VH, but not intra-DH, microinjection of 2.5 nmol H-89 increased the percentages of open arm entries and time spent in the open arms. Microinjection of 2.5 and 5.0 nmol H-89 reduced the frequency of protected head dipping behavior. Conclusions This study demonstrated that VH modulates anxiety-like behaviors in EPM. Moreover, CRF and the cAMP/PKA pathway seem to modulate these effects.
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关键词
Anxiety, Corticotropin-releasing factor, CRF1 receptor, Protein kinase A, Hippocampus, Elevated plus maze
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