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.
Changes in GABAA receptors and neurosteroid concentrations in the rat brain induced by corticotropin releasing factor (CRF)
Porcu P;
1998
Abstract
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
