Doxapram causes panic anxiety in humans. To determine whether doxapram alters corticotropin-releasing factor (CRF) expression in the central nucleus of the amygdala (CeA), paraventricular nucleus of hypothalamus (PVN), or bed nucleus of the stria terminalis (BNST), we used immunohistochemistry to measure CRF peptide in these brain areas after doxapram injection. Doxapram injection significantly increased CRF-like immunoreactivity (CRF-IR) within the CeA, but not in the BNST or PVN, and this increase was significant 2 h after injection. In addition, doxapram significantly increased CRF mRNA expression within the CeA, and this was most prominent 30 min after injection. These results suggest that doxapram selectively increases CRF expression within the CeA, and that this is mediated by increased CRF gene transcription. This increase in CRF-IR within the CeA might explain the doxapram-induced anxiety reaction.
Bibliographical noteFunding Information:
This research was supported by a grant from the Brain Research Center of the 21st Century Frontier Research Program, funded by the Korean Ministry of Science and Technology (Grant No. M103KV010007 03K2201 00720). We thank Dr. Younglim Lee (Indiana University, Indianapolis, IN, USA) for helpful suggestions and a review of the manuscript. We are grateful to professor Kelly Mayo for his kind gift of full-length rat CRF cDNA.
- Corticotropin-releasing factor
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience