Repeated maternal glucocorticoid treatment affects activity and hippocampal NMDA receptor expression in juvenile guinea pigs.
The behavioural consequences of prenatal glucocorticoid exposure are not well understood, though emerging studies in humans indicate hyperactivity and altered cognitive development can occur. Further, recent reports indicate that N-methyl-d-aspartate receptors (NMDARs) may mediate the development of postnatal stress behaviours. We hypothesized that prenatal betamethasone (Beta) administration would alter behaviour and the expression of hippocampal NMDAR subunits NR1, NR2A and NR2B in juvenile guinea pig offspring. We found that repeated maternal Beta (1 mg kg(-1)) treatment on gestational days (gd) 40/41, 50/51 and 60/61 (term approximately 70 days) had no significant effect on birthweight or early growth. However, Beta produced sex-specific effects on open-field activity and hippocampal NMDAR subunit expression compared with controls. Female Beta offspring exhibited significantly increased locomotor activity while there was no effect in Beta males. Beta males exhibited a tendency for decreased anxiety-like behaviour. With respect to NMDAR subunit expression, Beta-exposed females exhibited significantly reduced NR1 mRNA in CA1/2 and CA3 subfields of the hippocampus; there were no effects in Beta males. In conclusion, repeated maternal treatment with Beta, in a similar regimen to that administered to pregnant women at risk of delivering preterm, has profound consequences on behaviour and development of crucial neurotransmitter systems in postnatal life.
Owen
Dawn
D
Department of Physiology, Faculty of Medicine, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8.
Matthews
Stephen G
SG
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001623:Betamethasone / Q000494:pharmacology; D001724:Birth Weight / Q000187:drug effects; D015153:Blotting, Western; D001921:Brain / Q000254:growth & development; D001923:Brain Chemistry / Q000187:drug effects; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism*; D017403:In Situ Hybridization; D008098:Litter Size / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; C409466:NR1 NMDA receptor; C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D001623:Betamethasone