Doxapram increases corticotropin-releasing factor immunoreactivity and mRNA expression in the rat central nucleus of the amygdala.
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 2h after injection. In addition, doxapram significantly increased CRF mRNA expression within the CeA, and this was most prominent 30min 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.
Choi
Song-hyen
SH
Department of Pharmacology, Korea University College of Medicine, Sungbuk-gu, Anam-dong 5-ga 126-1, Seoul 136-705, Republic of Korea.
Kim
Sung-Jin
SJ
Park
Sang-Ha
SH
Moon
Bo-Hyun
BH
Do
Eunju
E
Chun
Boe-Gwun
BG
Lee
Min-Soo
MS
Shin
Kyung-Ho
KH
D000679:Amygdala / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000009:adverse effects*; D003346:Corticotropin-Releasing Hormone / Q000096:biosynthesis*; D004315:Doxapram / Q000008:administration & dosage / Q000009:adverse effects*; D005786:Gene Expression Regulation / Q000187:drug effects*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D016584:Panic Disorder / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012686:Septal Nuclei / Q000378:metabolism / Q000473:pathology
D000697:Central Nervous System Stimulants; D012333:RNA, Messenger; D003346:Corticotropin-Releasing Hormone; D004315:Doxapram