Prenatal betamethasone exposure has sex specific effects in reversal learning and attention in juvenile baboons

• Published in: American journal of obstetrics and gynecology Vol. 204; no. 6; pp. 545.e1 - 545.e10
• Main Authors: Rodriguez, Jesse S., PhD, Zürcher, Nicole R., MS, Keenan, Kathryn E., PhD, Bartlett, Thad Q., PhD, Nathanielsz, Peter W., MD, PhD, Nijland, Mark J., PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2011
• Subjects: Animals; Attention - drug effects; Betamethasone - adverse effects; developmental programming; Female; Glucocorticoids - adverse effects; Male; neurodevelopment; neuropsychological testing; nonhuman primates; Obstetrics and Gynecology; operant conditioning; Papio; Pregnancy; Prenatal Exposure Delayed Effects; Reversal Learning - drug effects; Sex Factors; synthetic glucocorticoids; synthetic glucocorticoids; neuropsychological testing; nonhuman primates; neurodevelopment; operant conditioning; developmental programming
• ISSN: 0002-9378; 1097-6868
• DOI: 10.1016/j.ajog.2011.01.063

Objective We investigated effects of 3 weekly courses of fetal betamethasone (βM) on motivation and cognition in juvenile baboon offspring utilizing the Cambridge Neuropsychological Test Automated Battery. Study Design Pregnant baboons ( Papio species) received 2 injections of saline control or 175 μg/kg βM 24 hours apart at 0.6, 0.65, and 0.7 gestation. Offspring (saline control female, n = 7 and saline control male, n = 6; βM female [FβM], n = 7 and βM male [MβM], n = 5) were studied at 2.6-3.2 years with a progressive ratio test for motivation, simple discriminations and reversals for associative learning and rule change plasticity, and an intra/extradimensional set-shifting test for attention allocation. Results βM exposure decreased motivation in both sexes. In intra/extradimensional testing, FβM made more errors in the simple discrimination reversal (mean difference of errors [FβM – MβM] = 20.2 ± 9.9; P ≤ .05), compound discrimination (mean difference of errors = 36.3 ± 17.4; P ≤ .05), and compound reversal (mean difference of errors = 58 ± 23.6; P < .05) stages as compared to the MβM offspring. Conclusion This central nervous system developmental programming adds growing concerns of long-term effects of repeated fetal synthetic glucocorticoid exposure. In summary, behavioral effects observed show sex-specific differences in resilience to multiple fetal βM exposures.