Effect of glucocorticoids on the adrenocortical axis responses to electrical stimulation of the amygdala and the ventral noradrenergic bundle.
In the present study we examined the negative feedback effect of exogenous and endogenous glucocorticoids (GC) on the responses of the hypothalamo-pituitary-adrenocortical (HPA) axis to electrical stimulation of the central amygdaloid nucleus (AMG) and the ventral noradrenergic bundle (VNAB). Injection of dexamethasone (DEX 5-50 microg/kg BW) 3.5 h prior to the electrical stimuli inhibited the serum ACTH and corticosterone (CS) responses in a dose dependent manner. At a dose of 50 microg/kg BW DEX, the stress induced responses was completely abolished. Pretreatment with a subcutaneous injection of corticosteroid type II receptor antagonist (RU-38486) 30 mg/kg BW, enhanced the ACTH and CS responses to both stimuli. In contrast, the type I receptor antagonist (RU-28381) did not affect neither the responses to both stimuli nor the inhibitory effect exerted by DEX. Electrical stimulation of both the AMG and VNAB caused a significant depletion of CRF-41 content of the median eminence (ME). Pretreatment with DEX (50 microg/kg BW) inhibited the electrical stimuli-induced depletion of ME CRH-41. These results suggest that: (1) the HPA axis responses to electrical stimuli of the AMG and the VNAB are sensitive to the negative feedback of GC; (2) the feedback effect exerted by GC is mediated by type II GC receptors; (3) CRH-41 released from the ME plays a dynamic role in mediating pituitary-adrenocortical responses to the electrical stimuli; (4) the inhibitory effect of exogenous DEX is mediated by a reduction of CRF-41 release from the ME.
Weidenfeld
J
J
Department of Neurology, Hadassah University Hospital, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Itzik
A
A
Feldman
S
S
D000302:Adrenal Cortex / Q000502:physiology; D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism; D000679:Amygdala / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D003345:Corticosterone / Q000097:blood / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004558:Electric Stimulation; D005246:Feedback; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000502:physiology*; D008297:Male; D015735:Mifepristone / Q000494:pharmacology; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D013148:Spironolactone / Q000031:analogs & derivatives / Q000494:pharmacology
D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D015735:Mifepristone; C041006:RU 28318; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone