Decreased marble burying behavior in female mice lacking neuromedin-B receptor (NMB-R) implies the involvement of NMB/NMB-R in 5-HT neuron function.
Neuromedin B (NMB) is a mammalian bombesin-like peptide distributed widely in the central nervous system. This peptide exerts its function via the NMB receptor (NMB-R). Female NMB-R-deficient mice were used to study the role that NMB/NMB-R may play in 5-HT neuron function since this relationship was suggested in previous in vitro studies. As 5-HT neurons are thought to modulate marble burying behavior, a role for NMB-R in this behavior was assessed. Relative to wild-type mice, NMB-R-deficient mice showed decreased marble burying behavior. However, depletion of 5-HT by treatment with p-chlorophenylalanine (p-CPA) increased burying behavior in NMB-R-deficient mice suggesting that increased levels of 5-HT in the brain cause a decrease in burying behavior in NMB-R-deficient mice. While HPLC analysis showed that 5-HT content in the whole brain does not differ between NMB-R-deficient and wild-type mice, an immunohistochemical analysis of brain sections showed that 5-HT expression in the dorsal raphe (DR) nucleus is elevated in NMB-R-deficient mice. Furthermore, a quantitative RT-PCR analysis revealed that 5-HT(1A)-receptor gene expression is downregulated in NMB-R-deficient mice at the whole brain level. These behavioral and biological results suggest that NMB/NMB-R may modulate 5-HT neuronal activity by affecting DR function.
Yamada
Kazuyuki
K
Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8502, Japan. yamada@ncnp.go.jp
Wada
Etsuko
E
Yamano
Mariko
M
Sun
Ying-Jie
YJ
Ohara-Imaizumi
Mica
M
Nagamatsu
Shinya
S
Wada
Keiji
K
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D010134:Fenclonine / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics; D015287:Neurokinin B / Q000031:analogs & derivatives* / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011903:Raphe Nuclei / Q000378:metabolism* / Q000503:physiopathology; D018004:Receptors, Bombesin / Q000172:deficiency* / Q000235:genetics; D011985:Receptors, Serotonin / Q000235:genetics; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin / Q000172:deficiency*; D012702:Serotonin Antagonists / Q000494:pharmacology
D012333:RNA, Messenger; D018004:Receptors, Bombesin; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D012701:Serotonin; D015287:Neurokinin B; C038393:neuromedin B; D010134:Fenclonine