Effects of developmental stress and lead (Pb) on corticosterone after chronic and acute stress, brain monoamines, and blood Pb levels in rats

Abstract

Despite restrictions, exposure to lead (Pb) continues. Moreover, exposure varies and is often higher in lower socioeconomic status (SES) families and remains a significant risk to cognitive development. Stress is another risk factor. Lower SES may be a proxy for stress in humans. When stress and Pb co-occur, risk may be increased. A few previous experiments have combined Pb with intermittent or acute stress but not with chronic stress. To determine if chronic developmental stress affects outcome in combination with Pb, we tested such effects on growth, organ weight, brain monoamines, and response to an acute stressor. Sprague Dawley rats were gavaged with Pb acetate (1 or 10 mg/kg) or vehicle every other day from postnatal day (P)4-29 and reared in standard or barren cages. Subsets were analyzed at different ages (P11, 19, 29). Chronic stress did not alter blood Pb levels but altered HPA axis response during early development whereas Pb did not. Pb treatment and rearing each altered organ-to-body weight ratios, most notably of thymus weights. Both Pb and rearing resulted in age- and region-dependent changes in serotonin and norepinephrine levels and in dopamine and serotonin turnover. The model introduced here may be useful for investigating the interaction of Pb and chronic developmental stress.

Figure 1

Mean ± SEM plasma concentrations of CORT both before and after an acute stressor (SWS) at different ages: A) P11, B) P19, and C) P29. ^*p < 0.05, ^**p < 0.01, ^***p < 0.001 vs. basal CORT levels within rearing conditions; bars indicate significant differences between rearing conditions ⁺p < 0.05, ⁺⁺⁺p < 0.001 vs. basal levels; ^#p < 0.05 vs. 30 min; ^$p < 0.05 vs. 60 min.

Figure 2

Mean ± SEM blood Pb (BPb) levels on P29. No effects of chronic stress were found. ^***p < 0.001 vs. vehicle control; ⁺⁺⁺p < 0.001 vs. 1 mg/kg Pb; ^###p < 0.001 vs. 10 mg/kg Pb.

Figure 3

Hypothalamic NE levels (pg/mg tissue) expressed as mean ± SEM as an effect of rearing condition in A) males and B) females in order to show the Sex × Rearing × Age effect. Effect of Pb exposure in C) males and D) females in order to show the Sex × Treatment × Age effect. ^*p < 0.05, ^**p < 0.01.

Figure 4

Hypothalamic 5-HIAA levels (pg/mg tissue) expressed as mean ± SEM. Left, effect of rearing condition after A) Na acetate (control), B) 1 mg/kg Pb, or C) 10 mg/kg Pb on P11, P19, and P29 to show the Treatment × Rearing × Age effect. Right, effect of Pb treatment and sex in those reared in D) standard-reared and E) barren-reared conditions to show the Sex × Treatment × Rearing effect. ^*p < 0.05 vs. respective vehicle control.

Figure 5

Hippocampal 5-HT and 5-HIAA levels (pg/mg tissue) expressed as mean ± SEM. Left, 5-HT in each rearing condition following A) Na acetate, B) 1 mg/kg Pb acetate, and C) 10 mg/kg Pb acetate to show the Treatment × Rearing × Age effect. Right, hippocampal 5-HIAA levels for each treatment group at each age examined in D) males and E) females to show the Sex × Treatment × Age effect. ^**p < 0.01, ^***p < 0.001.