Increase in cortical and midbrain tryptophan hydroxylase activity by intracerebroventricular administration of corticotropin releasing factor: block by adrenalectomy, by RU 38486 and by bilateral lesions to the central nucleus of the amygdala

Neurochem Int. 1992 Jan;20(1):81-92. doi: 10.1016/0197-0186(92)90129-f.

Abstract

Corticotropin releasing factor (CRF) infused bilaterally into the lateral ventricles of awake, chronically cannulated, male Sprague-Dawley rats produced a dose-dependent increase in the in vitro activity of cortical and midbrain tryptophan hydroxylase after 60 min. The maximal increase in enzyme activity of 60% over that of vehicle-treated controls was reached 45 min after an infusion of 3 micrograms CRF. The increase in enzyme activity after a single dose of CRF resembled that seen after exposure of rats to an acute sound stress: it was reversed by preincubation of the enzyme preparation with alkaline phosphatase and was nonadditive with the increase in activity obtained in the presence of phosphorylating conditions. The response to intracerebroventricularly administered CRF was abolished by bilateral adrenalectomy, but restored by repeated daily systemic administration of the synthetic glucocorticoid, dexamethasone (500 micrograms/day, i.p. for 3 days), to the adrenalectomized rats. Intracerebroventricular administration of the glucocorticoid antagonist, RU 38486 (200 micrograms/day for 4 days), also blocked the acute increase in tryptophan hydroxylase activity in response to CRF. Finally, bilateral lesions to the central nucleus of the amygdala, a region involved in mediating behavioral, endocrine and autonomic responses to stressful stimuli, abolished the increase in enzyme activity in response to intraventricular CRF. The glucocorticoid sensitivity of the response to CRF, as well as the involvement of the central nucleus of the amygdala support the view that CRF may have a role in mediating the enhancement of tryptophan hydroxylase activity by acute sound stress.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenalectomy*
  • Amygdala / physiology*
  • Analysis of Variance
  • Animals
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / enzymology*
  • Cerebral Ventricles / drug effects
  • Cerebral Ventricles / physiology*
  • Corticotropin-Releasing Hormone / administration & dosage
  • Corticotropin-Releasing Hormone / antagonists & inhibitors
  • Corticotropin-Releasing Hormone / pharmacology*
  • Dexamethasone / pharmacology
  • Infusions, Parenteral
  • Male
  • Mesencephalon / drug effects
  • Mesencephalon / enzymology*
  • Mifepristone / administration & dosage
  • Mifepristone / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Reference Values
  • Tryptophan Hydroxylase / metabolism*

Substances

  • Mifepristone
  • Dexamethasone
  • Corticotropin-Releasing Hormone
  • Tryptophan Hydroxylase