NPY exerts several biological actions in CNS via the activation of receptor subtypes named Y1R, Y2R, Y4R, Y5R. The intracerebroventricular administration of NPY elicits an anxiolytic effect in several animal models and NPY knock-out mice develop an anxiogenic behaviour. NPY also inhibits the anxiogenic effect of CRH, suggesting that they may act as functional antagonists in limbic regions. NPY is co-express with GABA in the amygdala and they may interact in the regulation of emotional behaviour. Y1R and Y5R coexist in the same neurons of several limbic and hypothalamic nuclei and they both might be involved in the anxiolytic and antistress effects of NPY. We have investigated the role of NPY-Y1R neurotransmission and its interaction with CRH and GABAergic system in the emotional response to group housing, as a model of chronic stress exposure. At this purpose, we used conditional knockout male mice (Y1R Y5R-/-) in which Y1R function is postnatally inactivated in Y5R expressing neurons, by using the doxicycline-controlled Cre/loxP system. Group-housing induced an anxious behaviour in control (Y1RloxP/LoxP) and Y1R Y5R-/- mice, as compared to socially isolated mice. In the elevated plus-maze test, there was a significant effect of housing conditions for percentage of time spent and percentage of entries into the open arms. The anxious behaviour of group-housed mice was also associated with an increase of cerebrocortical neuroactive steroids concentrations and a decrease of CRH immunoreactive fibers in the central amydala. Socially isolated Y1R Y5R-/- mice also showed an anxious behaviour, as compared to social isolated Y1RloxP/LoxP mice. Conversely, conditional deletion of Y1R failed to affect neuroactive steroids concentrations and CRH immunoreactivity. These data suggest that activation of Y1R, but not Y5R, may be involved in development of anxiety in response to group-housing, whereby a mechanism that appears to be independent on GABAergic or CHR pathways.
Role of NPY-Y1R transmission on stress response induced by group-housing in a model of conditional knock-out mice
LONGO, ANGELA;OBERTO, Alessandra;BERTOCCHI, Ilaria;MELE, PAOLO;EVA, Carola Eugenia
2010-01-01
Abstract
NPY exerts several biological actions in CNS via the activation of receptor subtypes named Y1R, Y2R, Y4R, Y5R. The intracerebroventricular administration of NPY elicits an anxiolytic effect in several animal models and NPY knock-out mice develop an anxiogenic behaviour. NPY also inhibits the anxiogenic effect of CRH, suggesting that they may act as functional antagonists in limbic regions. NPY is co-express with GABA in the amygdala and they may interact in the regulation of emotional behaviour. Y1R and Y5R coexist in the same neurons of several limbic and hypothalamic nuclei and they both might be involved in the anxiolytic and antistress effects of NPY. We have investigated the role of NPY-Y1R neurotransmission and its interaction with CRH and GABAergic system in the emotional response to group housing, as a model of chronic stress exposure. At this purpose, we used conditional knockout male mice (Y1R Y5R-/-) in which Y1R function is postnatally inactivated in Y5R expressing neurons, by using the doxicycline-controlled Cre/loxP system. Group-housing induced an anxious behaviour in control (Y1RloxP/LoxP) and Y1R Y5R-/- mice, as compared to socially isolated mice. In the elevated plus-maze test, there was a significant effect of housing conditions for percentage of time spent and percentage of entries into the open arms. The anxious behaviour of group-housed mice was also associated with an increase of cerebrocortical neuroactive steroids concentrations and a decrease of CRH immunoreactive fibers in the central amydala. Socially isolated Y1R Y5R-/- mice also showed an anxious behaviour, as compared to social isolated Y1RloxP/LoxP mice. Conversely, conditional deletion of Y1R failed to affect neuroactive steroids concentrations and CRH immunoreactivity. These data suggest that activation of Y1R, but not Y5R, may be involved in development of anxiety in response to group-housing, whereby a mechanism that appears to be independent on GABAergic or CHR pathways.
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