Behavioral changes in aging but not young mice after neonatal exposure to the polybrominated flame retardant decaBDE

Abstract

Background: After several decades of commercial use, the flame-retardant chemicals polybrominated diphenyl ethers (PBDEs) and their metabolites are pervasive environmental contaminants and are detected in the human body. Decabrominated diphenyl ether (decaBDE) is currently the only PBDE in production in the United States.

Objectives: Little is known about the health effects of decaBDE. In the present study we examined the effects of neonatal decaBDE exposure on behavior in mice at two ages.

Methods: Neonatal male and female C57BL6/J mice were exposed to a daily oral dose of 0, 6, or 20 mg/kg decaBDE from postnatal days 2 through 15. Two age groups were examined: a cohort that began training during young adulthood and an aging cohort of littermates that began training at 16 months of age. Both cohorts were tested on a series of operant procedures that included a fixed-ratio 1 schedule of reinforcement, a fixed-interval (FI) 2-min schedule, and a light-dark visual discrimination.

Results: We observed minimal effects on the light-dark discrimination in the young cohort, with no effects on the other tasks. The performance of the aging cohort was significantly affected by decaBDE. On the FI schedule, decaBDE exposure increased the overall response rate. On the light-dark discrimination, older treated mice learned the task more slowly, made fewer errors on the first-response choice of a trial but more perseverative errors after an initial error, and had lower latencies to respond compared with controls. Effects were observed in both dose groups and sexes on various measures.

Conclusions: These findings suggest that neonatal decaBDE exposure produces effects on behavioral tasks in older but not younger animals. The behavioral mechanisms responsible for the pattern of observed effects may include increased impulsivity, although further research is required.

Keywords: C57BL6 mouse; PBDE; behavior; behavioral effects; decabrominated diphenyl ether; fixed interval; fixed ratio; impulsivity; neonatal exposure; perseveration; visual discrimination.

Figure 1

Number of earned food pellets (mean ± SE) among control and decaBDE-treated mice (low dose, 6 mg/kg; high dose, 20 mg/kg) across the 10 sessions of the FR1 procedure in the young cohort (A) and the aging cohort (B). Male and female data were averaged within each litter.

Figure 2

FI overall response rate (A, B) and IOC(C,D) among control and decaBDE-treated mice (low dose, 6 mg/kg; high dose, 20 mg/kg) across the 60 sessions of the FI procedure in the young cohort (A,C) and aging cohort(B,D). Values are mean ± SE. Each session block is the mean of five consecutive sessions; male and female data were averaged within each litter.

Figure 3

Total number of errors (mean ± SE) among control and decaBDE-treated mice (low dose, 6 mg/kg; high dose, 20 mg/kg) across 41 sessions of the visual discrimination procedure in the young (A) and aging (B) cohorts. Male and female data were averaged within each litter. In the young cohort, the vertical line at the 18th session indicates the last session that included all of the subjects. After session 18, young subjects began to reach the criterion for the reversal procedure.

Figure 4

Number of first-choice errors (mean ± SE) among control and decaBDE-treated mice (low dose, 6 mg/kg; high dose, 20 mg/kg) in the visual discrimination procedure in the young(A, C) and aging(B, D) cohorts by sex. Because there was an exposure-by-sex interaction, females and males were analyzed separately. In the young cohort data plots, the vertical bar at the 18th session marks the last session that included all of the subjects.

Figure 5

Number of perseverative errors (mean ± SE) among control and decaBDE-treated mice (low dose, 6 mg/kg; high dose, 20 mg/kg) across the visual discrimination procedure in the young (A) and aging (B) cohorts. Male and female data were averaged within each litter. In the young cohort data plot, the vertical line at the 18th session marks the last session that included all of the subjects.

Figure 6

Latency to respond (mean ± SE) among control and decaBDE-treated mice (low dose, 6 mg/kg; high dose, 20 mg/kg) across the visual discrimination procedure in the young (A,C) and aging(B,D) cohorts by sex. Because there was an exposure-by-sex interaction, females and males were analyzed separately. In the young cohort (A,C), the vertical line at the 18th session marks the last session that included all of the subjects.