Modulation of 5-HT system in mice with a targeted disruption of neuromedin B receptor.
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.
Yamano
Mariko
M
Osaka Prefectural College of Health Sciences, Habikino, Osaka, Japan.
Ogura
Hiroo
H
Okuyama
Shigeru
S
Ohki-Hamazaki
Hiroko
H
D000818:Animals; D003345:Corticosterone / Q000097:blood; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D011903:Raphe Nuclei / Q000378:metabolism; D018004:Receptors, Bombesin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012149:Restraint, Physical; D012701:Serotonin / Q000378:metabolism*; D013312:Stress, Physiological / Q000378:metabolism
D016760:Proto-Oncogene Proteins c-fos; D018004:Receptors, Bombesin; D012701:Serotonin; D003345:Corticosterone