Pentobarbital attenuates stress-induced increases in noradrenaline release in specific brain regions of rats.
To examine whether anxiolytic action of drugs acting at the GABA/BZD-chloride channel complex may be related to the brain noradrenergic system, we investigated the effect of pentobarbital, a typical barbiturate which has potent GABA modulating properties, on increased NA release in nine brain regions of stressed rats. Pentobarbital (10 and 25 mg/kg) was injected IP 65 min before sacrifice (5 min before one-hour immobilization stress). Levels of 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MHPG-SO4), the major metabolite of brain noradrenaline (NA), and of plasma corticosterone, were fluorometrically determined. Pentobarbital treatment by itself increased MHPG-SO4 levels in the thalamus, locus coeruleus (LC) region, midbrain and basal ganglia of nonstressed rats. Stress produced increases in MHPG-SO4 levels in all brain regions examined and elevation of plasma corticosterone levels. Pentobarbital attenuated, in a dose-dependent manner, stress-induced increases in MHPG-SO4 levels in the hypothalamus, thalamus, anterior cerebral cortex, LC region and basal ganglia and also attenuated the stress-induced elevation of plasma corticosterone levels. These data suggest that pentobarbital can attenuate both stress-induced increases in NA release in specific brain regions as well as activation of the hypothalamo-pituitary-adrenocortical system. These attenuating effects may be related to the anxiolytic action of barbiturates.
Ida
Y
Y
Department of Pharmacology, Kurume University School of Medicine, Japan.
Tsuda
A
A
Tsujimaru
S
S
Satoh
M
M
Tanaka
M
M
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D003345:Corticosterone / Q000097:blood; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D010424:Pentobarbital / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013312:Stress, Physiological / Q000378:metabolism*
D008734:Methoxyhydroxyphenylglycol; D010424:Pentobarbital; D003345:Corticosterone; D009638:Norepinephrine