Gestational dexamethasone treatment elicits sex-dependent alterations in locomotor activity, reward-based memory and hippocampal cholinergic function in adolescent and adult rats.
Glucocorticoids are the consensus treatment for preventing respiratory distress syndrome in preterm infants but there is emerging evidence of subsequent neurobehavioral abnormalities, independent of somatic growth effects. Pregnant rats were given 0.2 mg/kg of dexamethasone, a dose commensurate with clinical use, on gestational days 17-19 and behavioral evaluations were made on the offspring in adolescence and adulthood. The dexamethasone groups had the same body weights as the controls but nevertheless displayed long-term, sex-selective alterations in locomotor and cognitive behaviors. In the figure-8 activity apparatus, dexamethasone treatment ablated the normal sex differences in locomotor activity by reducing values in females to the lower level typical of males; habituation of activity similarly was impaired in females, reducing the profile to match that of control males, while male rats in the dexamethasone group showed a partially feminized pattern of habituation. In the 8-arm radial maze, control rats displayed typical sex differences, with male rats performing more accurately than females. Dexamethasone treatment eliminated this normal dichotomy, delaying learning in males while improving performance in females to the level normally seen in control males. Finally, we assessed hippocampal [3H]hemicholinium-3 binding as a biomarker for cholinergic synaptic activity, and again found loss of sex differences in the dexamethasone group: values in males were increased to the higher levels typical of females. These results indicate that gestational treatment with dexamethasone obtunds the normal sex differences in neurochemistry and behavior that are typically seen in adolescence in adulthood, thus producing sex-selective alterations in activity, learning, and memory.
Kreider
Marisa L
ML
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
Levin
Edward D
ED
Seidler
Frederic J
FJ
Slotkin
Theodore A
TA
D000109:Acetylcholine / Q000378:metabolism*; D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects*; D001522:Behavior, Animal / Q000187:drug effects; D018678:Cholinergic Agents / Q000493:pharmacokinetics; D003907:Dexamethasone / Q000009:adverse effects*; D005260:Female; D006426:Hemicholinium 3 / Q000493:pharmacokinetics; D006624:Hippocampus / Q000187:drug effects*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D009043:Motor Activity / Q000187:drug effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D012727:Sex Characteristics; D014316:Tritium / Q000493:pharmacokinetics
D018931:Antineoplastic Agents, Hormonal; D018678:Cholinergic Agents; D014316:Tritium; D006426:Hemicholinium 3; D003907:Dexamethasone; D000109:Acetylcholine