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 related to corticotropin releasing factor (CRF), injected into the basolateral nucleus of the amygdala (BLA) in male Wistar rats would result in an anxiogenic response as measured in the social interaction (SI) test. In addition, it was found that repeated injections of subthreshold doses of Ucn would 'prime' the animal's response. This 'priming' effect induces a sensitivity to sodium lactate infusions that results in a panic-like reaction. Currently, we examined the effects of the CRF(1) and CRF(2) 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 administration of Ucn, but was only able to partially antagonize the same response following 'priming' with Ucn. Furthermore, Asn administered either alone or prior to a sodium lactate infusion had no effect on the primed rat's behavior. Autoradiographic studies, in Ucn primed and sham-primed animals indicated no significant changes in [(125)I]-Sauvagine binding to CRF(1) and CRF(2) 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 anxiogenic responses due to sodium lactate infusions in 'primed' rats
Sajdyk
T J
TJ
Neuroscience Division, Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Gehlert
D R
DR
D000679:Amygdala / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001007:Anxiety / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D018019:Receptors, Corticotropin-Releasing Hormone / Q000187:drug effects / Q000378:metabolism; D019354:Sodium Lactate / Q000494:pharmacology; D054832:Urocortins
D018696:Neuroprotective Agents; D010446:Peptide Fragments; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; C104416:astressin; D003346:Corticotropin-Releasing Hormone; D019354:Sodium Lactate