Astressin, a corticotropin releasing factor antagonist, reverses the anxiogenic effects of urocortin when administered into the basolateral amygdala

Previous work in our laboratory has shown that Urocortin (Ucn), a peptide r elated to corticotropin releasing factor (CRF), injected into the basolater al nucleus of the amygdala (BLA) in male Wistar rats would result in an anx iogenic response as measured in the social interaction (SI) test. In additi on, it was found that repeated injections of subthreshold doses of Ucn woul d 'prime' the animal's response. This 'priming' effect induces a sensitivit y to sodium lactate infusions that results in a panic-like reaction. Curren tly, we examined the effects of the CRF1 and CRF2 antagonist Astressin (Asn )on the anxiety-like responses produced during 'priming' as well as during a sodium lactate infusion into 'primed' rats. The results showed that Asn ( 60 pmoles) was able to reverse the anxiogenic effects seen during acute adm inistration of Ucn, but was only able to partially antagonize the same resp onse following 'priming' with Ucn. Furthermore, Asn administered either alo ne or prior to a sodium lactate infusion had no effect on the printed wt's behavior. Autoradiographic studies, in Ucn primed and sham-primed animals i ndicated no significant changes in [I-125]-Sauvagine binding to CRF1 and CR F2 receptors in several brain regions. Thus, a 60 pmole dose of Asn blocks the effects of an acute injection of Ucn (100 pmoles), while only partially blocking the behavioral effects after repeated injections of subthreshold doses of Ucn (6 pmoles) are given. Furthermore, Asn has no effect on anxiog enic responses due to sodium lactate infusions in 'primed' rats (C) 2000 El sevier Science B.V. All rights reserved.