open access

https://hdl.handle.net/2115/44115

The Serotonergic Projection from the Median Raphe Nucleus to the Ventral Hippocampus is Involved in the Retrieval of Fear Memory Through the Corticotropin-Releasing Factor Type 2 Receptor

英語

median raphe nucleus

2010-05

Nature Publishing Group

Neuropsychopharmacology

35(6)

1271-1278

Several different studies have separately established that serotonin, corticotropin-releasing factor (CRF) receptors, and the hippocampus are involved in fear memory retrieval. The main aim of the present study is to connect these separate studies. To assess the levels of anxiety/fear, we employed the contextual fear-conditioning test and the elevated plus maze test as memory-dependent and -independent tasks, respectively. We injected CRF receptor antagonists or vehicle into the median raphe nucleus (MRN) 10 minutes before behavioral tests. As a result, 1000 ng of astressin 2B (CRF2 receptor antagonist), but not 250 ng of antalarmin (CRF1 receptor antagonist), significantly suppressed the expression rate of freezing behavior in the contextual fear-conditioning test. However, in the elevated plus maze test, there was no difference between astressin 2B-injected rats and saline-injected rats in the time spent in open arms. Neither the amount of exploratory behavior nor the moving distance in the EPM of astressin 2B-injected rats differed from that of vehicle-injected rats. Moreover, when we assessed the extracellular serotonin release in the ventral hippocampus in freely moving rats through in vivo microdialysis, it was shown that the blockade of the CRF2 receptor in the MRN suppressed serotonin release in the ventral hippocampus during fear memory retrieval. These results indicated that endogenous CRF and/or related ligands released in the MRN could activate the CRF2 receptor and stimulate serotonin release in the ventral hippocampus, thereby inducing fear memory retrieval.

学術雑誌論文

Accepted Manuscript

0893-133X