Sound stress activation of tryptophan hydroxylase blocked by hypophysectomy and intracranial RU 38486.
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 micrograms/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 glucocorticoids is required for the serotonergic response to sound stress. The glucocorticoid antagonist, RU 38486, given intracerebroventricularly (200 micrograms/day for 4-5 days) or bilaterally, into the region of the central nucleus of the amygdala (100 micrograms 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.
Singh
V B
VB
Department of Physiology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond 23298.
Corley
K C
KC
Krieg
R J
RJ
Phan
T H
TH
Boadle-Biber
M C
MC
D000161:Acoustic Stimulation / Q000009:adverse effects*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology; D003907:Dexamethasone / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D007016:Hypophysectomy; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology; D007276:Injections, Intraventricular; D008297:Male; D008636:Mesencephalon / Q000187:drug effects / Q000201:enzymology; D015735:Mifepristone / Q000008:administration & dosage / Q000494:pharmacology*; D009475:Neurons, Afferent / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013148:Spironolactone / Q000031:analogs & derivatives / Q000494:pharmacology; D013315:Stress, Psychological / Q000201:enzymology*; D014365:Tryptophan Hydroxylase / Q000378:metabolism*
D013148:Spironolactone; D015735:Mifepristone; C047175:7-propyl spirolactone; D003907:Dexamethasone; D014365:Tryptophan Hydroxylase