Corticotropin-releasing factor acts via a third ventricle site to reduce exploratory behavior in rats

Corticotropin-releasing factor (CRF, 20-25 ng) injected into the lateral or fourth ventricles of rats decreased exploratory behavior in the multicompartment testing chamber (MCC), as assessed by decreased mean contact times with novel stimuli. This result extends similar observations made previously in mice. To investigate the site of this action of CRF, cold cream plugs injected into the cerebral ventricles of rats were used to prevent access of the CRF to specific periventricular sites. When the cerebral aqueduct was blocked with cold cream, CRF injected into the lateral ventricle, but not the fourth ventricle, decreased exploratory behavior in the MCC. These results suggest that CRF does not act in the fourth ventricle to alter behavior in the MCC, and most likely acts in the lateral or third ventricles. Cold cream blocks within the third ventricle prevented the effect of lateral ventricle administration of CRF. The clearest effects were obtained when the anteroventral portion of the third ventricle (AV3V) had been coated with cold cream. This region, which contains the organum vasculosum laminae terminalis (OVLT), was the only region blocked that showed a significant statistical interaction between the cold cream block and the effect of CRF. This result suggests that the OVLT, or regions close to it, is the primary site of the behavioral action of CRF in the MCC. It is possible that the peptide could be taken up in this region and transported to another brain site.