Chlordiazepoxide attenuates stress-induced activation of neurons, corticotropin-releasing factor (CRF) gene transcription and CRF biosynthesis in the paraventricular nucleus (PVN).
Corticotropin-releasing factor (CRF) plays a role in coordinating endocrine, autonomic, and behavioral responses to stressful stimuli. Benzodiazepines exert many effects which oppose those of CRF, including anxiolysis and suppression of the pituitary-adrenal axis. In the present study, we employed in situ analysis of CRF heteronucleous RNA (hnRNA) and c-fos mRNA to assess stimulus-induced CRF gene transcription rate following stress and its modulation by chlordiazepoxide (CDP). Male albino rats were exposed to restraint stress for 30 min and sacrificed 30 and 120 min after the onset of stress. Either CDP or vehicle was given intraperitoneally 60 min before stress. To determine plasma ACTH levels by immunoradiometric assay, another group of rats was decapitated 10 min after the onset of restraint stress. Restraint stress induced rapidly and significantly c-fos mRNA and CRF hnRNA expression in the PVN at the 30 min time point. Increases in both RNA copies were significantly inhibited by administration of CDP at doses of 5 and 10 mg/kg. CRF mRNA concentrations were increased significantly in the PVN 120 min after stress and again, CDP attenuated significantly these increases in the PVN. The plasma ACTH increase in response to stress was inhibited significantly by CDP administration at every dose tested. CDP did not change CRF mRNA levels in the non-stressed animal.(ABSTRACT TRUNCATED AT 250 WORDS)
Imaki
T
T
Department of Medicine, Tokyo Women's Medical College, Japan.
Wang
X Q
XQ
Shibasaki
T
T
Harada
S
S
Chikada
N
N
Takahashi
C
C
Naruse
M
M
Demura
H
H
D000818:Animals; D001345:Autoradiography; D002707:Chlordiazepoxide / Q000494:pharmacology*; D003346:Corticotropin-Releasing Hormone / Q000096:biosynthesis* / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000235:genetics; D017403:In Situ Hybridization; D008016:Life Change Events; D008297:Male; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D014158:Transcription, Genetic
D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D002707:Chlordiazepoxide; D003346:Corticotropin-Releasing Hormone