NPY acts in the CNS to reduce behavioral physiological and endocrine responses to stressful stimuli via the activation of Y1 receptors. Exposure to 1-h restraint stress decreases NPY mRNA and protein content in the amygdala. Conversely exposure to restraint for 10 days increases NPY expression. Acute stress also reduces GABAA receptor function in several brain regions and increases neuroactive steroid brain concentrations to levels that activate GABAA receptors. GABA and NPY are functionally coupled and may act in concert to inhibit the excitatory effects of CRF in the amygdala. We previously showed that a sustained increase in the brain concentrations of neuroactive steroids, induced by various conditions, increases Y1 receptor gene expression in the amygdala of Y1R/LacZ transgenic mice harboring the Y1 receptor gene promoter/LacZ fusion gene. We now studied the effect of restraint stress on both the brain concentrations of neuroactive steroids and the Y1 receptor gene expression in the amygdala and paraventricular nucleus (PVN) of Y1R/LacZ mice. The cerebrocortical concentrations of allopregnanolone and allotetrahydrodeoxycorticosterone were significantly increased immediately after a 1-h exposure to restraint and had returned to control values within 30 min. Expression of Y1R/LacZ increased in the amygdala and PVN 6 h after restraint. The 5a-reductase inhibitor finasteride prevented the increase in neuroactive steroid concentrations but did not block that of transgene expression induced by a 1h-restraint. Daily exposure to restraint for 10 days also increased neuroactive steroid concentrations but did not affect transgene expression. Acute but not repeated restraint thus increases Y1 receptor gene expression in the amygdala and PVN suggesting that tolerance develops towards this stressor. This effect is not mediated by the increase in brain neuroactive steroids concentrations but may rather reflect a ligand-induced increase in Y1 receptor gene transcription.
Restraint stress increases Npy-Y1 receptor gene expression in the amygdala of Y1 receptor/Lacz transgenic mice
OBERTO, Alessandra;MELE, PAOLO;EVA, Carola Eugenia
2004-01-01
Abstract
NPY acts in the CNS to reduce behavioral physiological and endocrine responses to stressful stimuli via the activation of Y1 receptors. Exposure to 1-h restraint stress decreases NPY mRNA and protein content in the amygdala. Conversely exposure to restraint for 10 days increases NPY expression. Acute stress also reduces GABAA receptor function in several brain regions and increases neuroactive steroid brain concentrations to levels that activate GABAA receptors. GABA and NPY are functionally coupled and may act in concert to inhibit the excitatory effects of CRF in the amygdala. We previously showed that a sustained increase in the brain concentrations of neuroactive steroids, induced by various conditions, increases Y1 receptor gene expression in the amygdala of Y1R/LacZ transgenic mice harboring the Y1 receptor gene promoter/LacZ fusion gene. We now studied the effect of restraint stress on both the brain concentrations of neuroactive steroids and the Y1 receptor gene expression in the amygdala and paraventricular nucleus (PVN) of Y1R/LacZ mice. The cerebrocortical concentrations of allopregnanolone and allotetrahydrodeoxycorticosterone were significantly increased immediately after a 1-h exposure to restraint and had returned to control values within 30 min. Expression of Y1R/LacZ increased in the amygdala and PVN 6 h after restraint. The 5a-reductase inhibitor finasteride prevented the increase in neuroactive steroid concentrations but did not block that of transgene expression induced by a 1h-restraint. Daily exposure to restraint for 10 days also increased neuroactive steroid concentrations but did not affect transgene expression. Acute but not repeated restraint thus increases Y1 receptor gene expression in the amygdala and PVN suggesting that tolerance develops towards this stressor. This effect is not mediated by the increase in brain neuroactive steroids concentrations but may rather reflect a ligand-induced increase in Y1 receptor gene transcription.
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