Altered emotional behaviors in the diabetes mellitus OLETF type 1 congenic rat.
GPR10 is a G-protein-coupled receptor expressed in thalamic and hypothalamic brain regions, including the reticular thalamic nucleus (RTN) and periventricular nucleus (Pev), and the endogenous ligand for this receptor, prolactin-releasing peptide (PrRP), has demonstrated regulatory effects on the stress response. We produced a congenic rat by introducing the Dmo1 allele from the OLETF rat which encodes the amino acid sequences of GPR10 with a truncated NH2-terminus, into the Brown-Norway background. Using receptor autoradiography, we determined a lack of specific [125I]PrRP binding in the RTN and Pev of these mutant rats compared to the control rats. Furthermore, intracerebroventricular injection of PrRP did not induce a significant increase of c-fos-like immunoreactivity in the paraventricular nucleus of the mutant rats compared to the control rats. The mutant rats also displayed a less anxious-like phenotype in three behavioral-based models of anxiety-like behavior (open field, elevated plus maze and defensive withdrawal test). These data show the mutant congenic rat, of which GPR10 neither binds nor responds to PrRP, expresses less anxious-like phenotypes. On the basis of these observations, the GPR10 might be a novel target for the developing new drugs against anxiety and/or other stress-related diseases.
Watanabe
Akihito
A
Department of Molecular Neurobiology, Graduate School of Medicine, Kanazawa University, Kanazawa, 920-8640, Japan. a_watanabe@otsuka-europe.com
Okuno
Shiro
S
Okano
Mai
M
Jordan
Shaun
S
Aihara
Koutoku
K
Watanabe
Takeshi K
TK
Yamasaki
Yuki
Y
Kitagawa
Hisashi
H
Sugawara
Kiyoshi
K
Kato
Satoru
S
D000374:Aggression / Q000502:physiology; D000483:Alleles; D000818:Animals; D020296:Animals, Congenic; D001007:Anxiety / Q000235:genetics / Q000523:psychology; D001345:Autoradiography; D001522:Behavior, Animal / Q000502:physiology*; D001835:Body Weight / Q000502:physiology; D002940:Circadian Rhythm / Q000235:genetics / Q000502:physiology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000523:psychology*; D004644:Emotions / Q000502:physiology*; D005260:Female; D016762:Genes, fos / Q000502:physiology; D005819:Genetic Markers; D007276:Injections, Intraventricular; D008024:Ligands; D009043:Motor Activity / Q000502:physiology; D009474:Neurons / Q000378:metabolism; D051381:Rats; D020334:Rats, Inbred OLETF / Q000523:psychology*; D015398:Signal Transduction / Q000502:physiology
D005819:Genetic Markers; D008024:Ligands