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

Abstract

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.

Figure 1

Analysis of touch screen training (moving stimulus task) shows a treatment effect in the Female βM offspring (closed bar, n=7) increased percent error versus Female Control (open bar, n=7), but no effect between the male groups or between sex within treatment. Male Control (small squares, n=6) and Male βM (big squares, n=5). Mean ± SEM; p<0.05, *.

Figure 2

A) Analysis of progressive ratio responses during 10 sessions revealed no differences between treatment or sex. B) Pooled groups showed a borderline difference (p=0.09), βM exposed offspring responded less. Female Control (open bar, n=7), Female βM exposed (closed bar, n=7), Male Control (small squares, n=6) and Male βM exposed (big squares, n=5). Mean ± SEM.

Figure 3

A) Analysis of errors made during simple discrimination (SD) 1–5 tasks revealed a sex effect with the Female Control (open bars, n=7) making more errors than the Male Control (small squares, n=6) offspring during SD2 (p≤0.05, #). Female βM exposed (closed bars, n=7) and Male βM exposed (big squares, n=5). Mean ± SEM. B) Analysis of errors made during simple discriminations (SD) followed by reversals (SR) revealed a treatment effect with the Female βM exposed offspring (closed bars, n=7) making more errors than the Female Control (open bars, n=7) during SR2 (p<0.05, *) and a sex effect as compared to the Male βM exposed offspring (big squares, n=5) during SR1 and SR2 (p<0.05, #), and SR3 (p=0.07, †). Male Control (small squares, n=6). Mean ± SEM.

Figure 3

A) Analysis of errors made during simple discrimination (SD) 1–5 tasks revealed a sex effect with the Female Control (open bars, n=7) making more errors than the Male Control (small squares, n=6) offspring during SD2 (p≤0.05, #). Female βM exposed (closed bars, n=7) and Male βM exposed (big squares, n=5). Mean ± SEM. B) Analysis of errors made during simple discriminations (SD) followed by reversals (SR) revealed a treatment effect with the Female βM exposed offspring (closed bars, n=7) making more errors than the Female Control (open bars, n=7) during SR2 (p<0.05, *) and a sex effect as compared to the Male βM exposed offspring (big squares, n=5) during SR1 and SR2 (p<0.05, #), and SR3 (p=0.07, †). Male Control (small squares, n=6). Mean ± SEM.

Figure 4

Analysis of errors made in the stages of the Intra-/Extra-dimensional Attention Set Shifting test revealed a sex effect between the Female βM exposed (closed bars, n=7) and the Male βM exposed (big squares, n=5) offspring in the SR, CD, and CR stages (p≤0.05, #). Female βM offspring made more errors. Female Control (open bars, n=7) and Male Control (small squares, n=5). Mean ± SEM.