Involvement of corticosteroid-like neurosteroids in pentobarbital-induced sleep.
Recent reports have confirmed the involvement of neurosteroids in a number of neurophysiological processes, including sleep, and that these compounds interact with the gamma-aminobutyric acid receptor A complex. As many of the behavioural effects of pentobarbital are as a result of the activity at this complex, we investigated the role of corticosteroid-like neurosteroids in regulation of sleep, using metyrapone as a tool. Metyrapone, a blocker of the enzyme 11 beta-hydroxylase, which is essential for the biosynthesis of corticosteroids, when administered intracerebroventricularly (i.c.v.) at low doses (50-5000 ng) caused a dose-dependent reduction in sleep time induced by pentobarbital. This effect was, however, antagonized by concomitant administration of anti-corticotropin-releasing factor antisera. The present study reveals for the first time that corticosteroid-like neurosteroids might be involved in the regulation of CNS excitability.
Burade
V S
VS
Department of Pharmaceutical Sciences, Nagpur University Campus, India.
Jain
M R
MR
Khan
F A
FA
Saha
S G
SG
Subhedar
N
N
D000305:Adrenal Cortex Hormones / Q000502:physiology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006993:Hypnotics and Sedatives / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008297:Male; D008797:Metyrapone / Q000008:administration & dosage / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000502:physiology*; D010424:Pentobarbital / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012890:Sleep / Q000187:drug effects / Q000502:physiology*
D000305:Adrenal Cortex Hormones; D006993:Hypnotics and Sedatives; D018377:Neurotransmitter Agents; D010424:Pentobarbital; D008797:Metyrapone