| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2006: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2005: ¥3,200,000 (Direct Cost: ¥3,200,000)
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| Research Abstract |
The present study was undertaken to clarify the central mechanisms, involved in the intracerebroventricularly administered corticotropin-releasing factor-induced elevation of plasma corticosterone in urethane- and α-chloralose-anesthetized rats using microdialysis and immunohistochemical techniques. When corticotropin-releasing factor was given at 0.5,1.5,and 3.0 nmol/animal intracerebroventricularly, it dose-dependently increased noradrenaline release but not adrenaline release in the hypothalamic paraventricular nucleus. The 1.5 nmol/animal dose of corticotropin-releasing factor-induced noradrenaline release was attenuated by CP-154,526 (butyl-ethyl-{2,5-dimethy1-7-(2,4,6trimethylpheny1)-7H-pyrrolo [2,3-d] pyrimidin-4-yl} amine), a selective corticotropin-releasing factor 1 receptor antagonist, at 1.3 mol/animal, intracerebroventricularly, and was also abolished by phentolamine at 0.66 mol/animal, intracerebroventricularly. In addition, the corticotropin-releasing factor-induced elev
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ation of noradrenaline release in-the hypothalamic paraventricular nucleus and plasma corticosterone were abolished by hexamethonium, a nonselective nicotinic acetylcholine receptor antagonist, at 1.8 μmol/animal, intracerebroventricularly, and α-conotoxin MII, a potent α_3β_2 nicotinic acetylcholine receptor antagonist, at 30 nmol/animal, i.c.v. Corticotropin-releasing factor at 1.5 nmol/animal, i.c.v. evoked a significant expression of cFos, an immediate-early gene product, on the dopamine-β-hydroxylase-containing neurons and α_3 nicotinic acetylcholine receptor subunit-expressing neurons in the locus coeruleus, but not in the medullary A_1 and A_2 regions containing noradrenergic neurons. These results suggest that centrally administered corticotrophin-releasing factor elevates plasma corticosterone by the corticotropin-releasing factor 1 receptor and α_3 subunit-containing nicotinic acetylcholine receptor (probably α_3 β_2 nicotinic acetylcholine receptor) mediated activation of the locus coeruleus noradrenergic neurons projecting to the paraventricular nucleus in rats Less
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