Annals of the New York Academy of Sciences, Vol 496, Issue 1 450-458, Copyright © 1987 by New York Academy of Sciences
Effect of diazepam on brain neurotransmitters, plasma corticosterone, and the immune system of stressed rats
D. Pericic, H. Manev, M. Boranic, M. Poljak-Blazi and N. Lakic
Rats were treated with injections of diazepam (1 or 10 mg/kg) and stressed
by restraint lasting 3 hours. This was performed once or, in animals
immunized with sheep erythrocytes, repeatedly for 4 consecutive days. After
repeated stress and/or diazepam treatment, the levels of brain noradrenalin
decreased in all treated groups. Although both treatments (stress and
diazepam) diminished the 5-hydroxytryptamine (5-HT)/5-hydroxyindoleacetic
acid (5-HIAA) ratio, treatment with either dose of diazepam prevented the
stress-induced fall of this ratio. The activity of hypothalamic glutamate
decarboxylase, the enzyme taking part in GABA synthesis, was affected
neither by the acute nor by repeated stress and/or diazepam treatment. The
levels of plasma corticosterone were enhanced in all stressed rats, with
and without drug. This finding was in accordance with the enhanced weights
of adrenal glands in repeatedly stressed rats. The tendency to a
corticosterone rise after repeated treatment with diazepam, 10 mg/kg,
coincided with the enhanced weights of adrenal glands in these animals. The
plaque-forming cell (PFC) response was reduced in all stressed animals and
in animals treated with diazepam, 10 mg/kg. Accordingly, high doses of
diazepam given repeatedly to rats are immunosuppressive, achieving this
effect presumably by an enhancement of glucocorticoid secretion. Neither
the low nor the high doses of diazepam affect the stress-induced
enhancement of hypothalamohypophysial-adrenal axis activity and consecutive
immunosuppression.
