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Modulation of 5‐HT system in mice with a targeted disruption of neuromedin B receptor
Author(s) -
Yamano Mariko,
Ogura Hiroo,
Okuyama Shigeru,
OhkiHamazaki Hiroko
Publication year - 2002
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.10194
Subject(s) - endocrinology , dorsal raphe nucleus , medicine , serotonergic , raphe nuclei , corticosterone , hypothalamus , receptor , basal (medicine) , serotonin , biology , 5 ht receptor , wild type , chemistry , mutant , gene , hormone , insulin , biochemistry
To assess the role of neuromedin B receptor (NMB‐R) on the modulation of serotonergic (5‐HT) system, the function of the 5‐HT system was examined in mice lacking the NMB‐R gene. Immunohistochemical analysis of brain sections revealed that 5‐HT expression level in the dorsal raphe neurons was elevated in NMB‐R‐deficient mice compared with wild‐type mice. Although restraint stress enhanced 5‐HT expression in these neurons in wild‐type mice, this treatment did not affect 5‐HT expression level in NMB‐R‐deficient mice, indicating the modulation of 5‐HT system in the mutant mice. Since 5‐HT system is involved in responses to stress and anxiety, we characterized stress response in these mice. The number of c‐Fos expressing cells in the paraventricular nucleus of the hypothalamus was higher in NMB‐R‐deficient mice than in wild‐type mice in both basal and stressed conditions. Moreover, the plasma corticosterone level under restraint stress was elevated in NMB‐R‐deficient mice compared to wild‐type mice. In the forced swimming tests, the duration of immobility was longer in mutant mice than in wild‐type mice. These data show dysregulated response to stress in NMB‐R‐deficient mice. However, behavior related to anxiety, assessed by elevated plus‐maze and light‐dark box, was not affected in NMB‐R‐deficient mice. NMB‐R is known to be expressed in dorsal raphe neurons, and our data suggest that NMB‐R has an important role in fine tuning of subsets of 5‐HT neurons in this nucleus, and impairment of this system leads to the dysregulated response to stress. © 2002 Wiley‐Liss, Inc.