Perinatal treatment with glucocorticoids and the risk of maldevelopment of the brain.
Drugs administered during the perinatal period reach the developing organism at the vulnerable stage of intensive brain histogenesis and cytodifferentiation. They may interfere with the programme of developmental processes in the brain and lead to disturbances at the cellular/subcellular level and to biochemical alterations. These abnormalities form the basis for the functional pathology which becomes apparent gradually during maturation or even in adulthood as neuropsycho-behavioural deviations. A model experimental study in rats was carried out with synthetic glucocorticoids, which are widely used in obstetrics and neonatology for the prevention and treatment of neonatal idiopathic respiratory distress syndrome. As the developmental stage of the brain of the human foetus in late pregnancy closely resembles the ontogenetic phases of the brain of the rat in the early postnatal period, the neonate rat was taken as a model. The administration of dexamethasone to 7-day-old rats resulted in significant depletion of glucocorticoid receptors from the cytosol of the brain in a dose-dependent manner, beginning with the dose of 0.04 mg/kg (s.c.), i.e. a dose one order lower than the clinical dose used in obstetrics (0.4-0.5 mg/kg). Long-term follow-up of a single neonatal injection of dexamethasone (0.2 or 1 mg/kg s.c. on postnatal day 7) revealed an acceleration of some developmental landmarks in the preweaning period (incisor eruption, eye opening, motor skill) on the one hand, but a retardation of body growth and vaginal opening on the other hand. Adult animals exhibited a deficit in motor co-ordination, behavioural deviations (hyperactivity with stereotypy, decreased adaptability, increased emotional reactivity) and disturbances in reproduction in both males and females.(ABSTRACT TRUNCATED AT 250 WORDS)
Benesová
O
O
Psychiatric Research Institute, Prague, Czechoslovakia.
Pavlík
A
A
D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development*; D001362:Avoidance Learning / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000254:growth & development; D001923:Brain Chemistry; D003907:Dexamethasone / Q000009:adverse effects*; D007858:Learning / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012054:Reinforcement, Psychology; D012098:Reproduction / Q000187:drug effects
D003907:Dexamethasone