Sound stress activation of tryptophan hydroxylase blocked by hypophysectomy and intracranial RU 38486

Abstract

The rapidly reversible increase in cortical or midbrain tryptophan hydroxylase activity observed ex vivo after exposure of rats to 1-h sound stress was blocked by hypophysectomy, but not sham hypophysectomy, and restored by dexamethasone administration to the hypophysectomized animals (500 μg/day i.p. for 3 days). The response to sound stress was also lost with deafferentation of the hypothalamus. These results indicate that hypothalamic control of adrenal glucocorticoid is required for the serotoenergic response to sound stress. The glucocorticoid antagonist, RU 38486, given intracerebroventricularly (200 μg/day for 4–5 days) or bilaterally, into the region of the central nucleus of the amygdala (100 μg 15 min before stress), blocked the sound stress-induced increase in tryptophan hydroxylase activity. In contrast, the antimineralocorticoid, RU 26752, was without effect. The block obtained with RU 38486 suggests that glucocorticoid is required by the neurons that relay the effects of sound stress to the rostrally projecting serotonergic neurons.