Changes in GABAA receptors and neurosteroid concentrations in the rat brain induced by corticotropin releasing factor (CRF)

The time-related changes in brain GABAA receptor function and cerebrocortical concentration of neurosteroids induced by intracerebroventricular injection of CRF was investigated in rats. CRF (5 to 20 ug/5 ul) resulted in a dose-dependent increase in [35S]t-butylbicyclophosphorothionate (TBPS) binding to cerebrocortical membrane preparations from rats killed 5 min after injection. At doses of 5 and 10 ug, this peptide had no significant effect on [35S]TBPS binding, whereas 15 ug induced a 27% increase. A greater effect (+48 ± 6%) was apparent at a dose of 20 ug, while higher doses (25 to 50 ug) failed to further increase this parameter. The effect of CRF was maximal 5 min after injection, was still present (+20%) at 10 min and returned to control value by 15 min. The short-lasting effect of CRF is inhibited by a pre-administration of abecarnil, an anxiolytic beta-carboline derivative. ICV injection of CRF increased markedly brain progesterone and allopregnanolone which were maximally increased (+84 and +110%) 10 and 15 min following CRF injection and declined thereafter. Finally, the effect of CRF on [35S]TBPS binding as well as that on neurosteroid concentrations is not detected in adrenalectomised/orchietomised rats. The relationship between the activation of HPA axis and the changes in GABAergic transmission and brain and plasma neurosteroid concentrations will be discussed.