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Publication : Conditional inactivation of neuropeptide Y Y1 receptors unravels the role of Y1 and Y5 receptors coexpressing neurons in anxiety.

First Author  Longo A Year  2014
Journal  Biol Psychiatry Volume  76
Issue  11 Pages  840-9
PubMed ID  24548641 Mgi Jnum  J:207463
Mgi Id  MGI:5558959 Doi  10.1016/j.biopsych.2014.01.009
Citation  Longo A, et al. (2014) Conditional inactivation of neuropeptide Y Y1 receptors unravels the role of Y1 and Y5 receptors coexpressing neurons in anxiety. Biol Psychiatry 76(11):840-9
abstractText  BACKGROUND: The Y1 receptor (Y1R) and Y5 receptor (Y5R) for neuropeptide Y share similar actions in the regulation of anxiety. Previously demonstrated that conditional removal of the Y1R during postnatal development in the forebrain excitatory neurons leads to higher anxiety, increased hypothalamus-pituitary-adrenocortical axis activity, and decreased body growth rate in male mice raised by foster mothers that exhibit high levels of maternal care. In the present study, we used the same conditional system to analyze the specific contribution to emotional behavior and stress response of the Y1R coexpressed with the Y5R. METHODS: Using the Cre-loxP recombination system, we investigated anxious behavior, spatial memory, and metabolic functions of conditional knockout mice in which the inactivation of the Npy1r gene was induced in the Y5Rs expressing neurons of juvenile mice (Npy1r(Y5R-/-) ). RESULTS: Npy1r(Y5R-/-) mice show increased anxiety-related behavior but no changes in hypothalamus-pituitary-adrenocortical axis activity or in body weight growth, independently of gender and mouse strain used as foster mothers. Also, Npy1r(Y5R-/-) mice of both genders display increased spatial reference memory in the Morris water maze test. CONCLUSIONS: The results suggest that neuropeptide Y Y1R differentially expressed in the limbic system regulates anxiety and stress responses via distinct neurochemical circuits. In addition, we provide the first experimental genetic evidence that the Y1Rs coexpressed with the Y5R are involved in retention of spatial memory in male and female mice.
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