? Corticotropin Releasing Factor (CRF) is involved with stress responses and its dysfunction has been indicated in depression, anxiety disorders and drug addiction. CRF has also been implicated in complex interactions with the serotonergic system, which modulates a range of affective functions. The CRF system has significant developmental influences on normal affective functioning. This proposal will examine the respective roles of the CRF1 and CRF2 receptors using novel CRF receptor selective ligands to probe anxiety-like behavior in mice using the acoustic startle reflex (ASR). After determining the roles of each CRF receptor in CRF-potentiated ASR, response to CRF will be examined in serotonin 1A receptor knockout (KO) mice. Because the anxious-like phenotype of these mice is due to the loss of 5-HT1A receptors during development, it is hypothesized that the CRF system is altered in these mice, indicating an important developmental and functional link between these two systems. Preliminary evidence that 5-HT1A mice exhibit more CRF-potentiated ASR than wild-types supports this hypothesis. This project will examine potential mechanisms for the observed hyper-sensitivity to CRF in 5-HT1A KO mice. This information will contribute to knowledge of both normal CRF-5-HT1A receptor interactions in anxiety-like behavior as well as to the understanding of the developmental role of the 5-HT 1A receptor in CRF system function. ? ? ?
| Risbrough, Victoria B; Hauger, Richard L; Roberts, Amanda L et al. (2004) Corticotropin-releasing factor receptors CRF1 and CRF2 exert both additive and opposing influences on defensive startle behavior. J Neurosci 24:6545-52 |
