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Updated: Jul 30, 2026

Long-term Behavioral and Reproductive Consequences of Embryonic Exposure to Low-dose Toxicants
Published on: March 6, 2018
Fixed interval/fixed ratio performance in adult monkeys exposed in utero to methylmercury
S G Gilbert1, D C Rice, T M Burbacher
1Department of Environmental Health, University of Washington, Seattle 98105-6099, USA. sgg@u.washington.edu
Abstract:
Previous studies in monkeys and rodents have shown the fixed interval/fixed ratio (FI/FR) schedule to be a sensitive indicator of neurotoxicity. In the present study, monkeys (Macaca fascicularis) were exposed in utero to methylmercury (MeHg). Maternal doses of MeHg of 50, 70, or 90 micrograms/kg b.wt./day resulted in infant blood mercury levels at birth ranging from 1.04 to 2.45 ppm. Monkeys were tested on a multiple FI/FR schedule of reinforcement at 8-10 years of age. Four FI/FR cycles were run per session. Pause time and run rate were calculated for FI and FR components, as well as FI quarter-life and local FI response rates. MeHg treatment and sex effects were investigated by fitting a linear orthogonal polynomial regression to each monkey's profile across sessions and performing two-way ANOVAs on the resulting linear and intercept terms. There were no treatment-related effects on either the FI or FR component for pause time or run rate. Analysis of the quarter-life revealed a significant treatment by sex effect as well as a main effect for sex. Post hoc t-tests revealed a significant difference in quarter-life of treated male and female monkeys and a marginal difference between treated and control males. The FI run rate of the male monkeys was significantly greater than that of the female monkeys whereas the FR run rate of the males was marginally greater. These results indicate that there may be a differential effect of MeHg on male and female monkeys, which could be interpreted as an effect on temporal discrimination. Overall, adult monkeys exposed to in utero MeHg exhibited a very limited sex-related effects on the FI/FR intermittent schedule of reinforcement.
Insights
Prenatal methylmercury (MeHg) exposure in monkeys did not affect overall performance on fixed interval/fixed ratio (FI/FR) schedules. However, MeHg showed sex-related differences in temporal discrimination, impacting male and female monkeys differently.
Area of Science:
- Neuroscience
- Toxicology
- Behavioral Pharmacology
Background:
- Fixed interval/fixed ratio (FI/FR) schedules are sensitive indicators of neurotoxicity in animal models.
- Methylmercury (MeHg) is a known neurotoxin with potential developmental effects.
- Understanding the long-term behavioral consequences of in utero MeHg exposure is crucial.
Purpose of the Study:
- To investigate the long-term effects of in utero methylmercury (MeHg) exposure on adult monkeys (Macaca fascicularis).
- To assess neurotoxicity using a multiple fixed interval/fixed ratio (FI/FR) schedule of reinforcement.
- To examine potential sex-specific effects of MeHg exposure on behavioral measures.
Main Methods:
- Monkeys were exposed in utero to varying doses of methylmercury (MeHg).
- Adult offspring (8-10 years old) were tested on a multiple FI/FR schedule.
- Behavioral data (pause time, run rate, FI quarter-life) were analyzed using regression and ANOVA, considering treatment and sex effects.
Main Results:
- No significant treatment-related effects were observed on overall pause time or run rate in either FI or FR components.
- A significant treatment-by-sex interaction and a main effect of sex were found for FI quarter-life.
- Post hoc analyses revealed sex-specific differences in quarter-life and run rates, suggesting potential impacts on temporal discrimination.
Conclusions:
- In utero methylmercury (MeHg) exposure in adult monkeys resulted in limited sex-related behavioral effects on FI/FR schedules.
- MeHg exposure may differentially affect temporal discrimination in male and female monkeys.
- Further research is needed to elucidate the precise mechanisms underlying these sex-specific neurodevelopmental effects.

