Spatial and visual discrimination reversals in adult and geriatric rats exposed during gestation to methylmercury and n − 3 polyunsaturated fatty acids

Fish contain essential long chain polyunsaturated fatty acids (PUFAs), particularly docosahexaenoic acid (DHA), an omega-3 (or n − 3) PUFA, but are also the main source of exposure to methylmercury (MeHg), a potent developmental neurotoxicant. Since n − 3 PUFAs support neural development and functio...

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Published in:Neurotoxicology (Park Forest South) 2007-07, Vol.28 (4), p.707-719
Main Authors: Paletz, Elliott M., Day, Jeremy J., Craig-Schmidt, Margaret C., Newland, M. Christopher
Format: Article
Language:English
Subjects:
Aging
Aging - drug effects
Aging - physiology
Animals
Animals, Newborn
Biological and medical sciences
Chemical and industrial products toxicology. Toxic occupational diseases
Development
Discrimination Learning - drug effects
Discrimination reversal
Fatty Acids, Omega-3
Female
Fish oil
Functional Laterality - drug effects
Male
Medical sciences
Metals and various inorganic compounds
Methylmercury
Methylmercury Compounds
Multivariate Analysis
Operant behavior
Photic Stimulation - methods
Pregnancy
Prenatal Exposure Delayed Effects - chemically induced
Prenatal Exposure Delayed Effects - physiopathology
PUFA
Rats
Rats, Long-Evans
Reversal Learning - drug effects
Space Perception - drug effects
Toxicology
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Summary:Fish contain essential long chain polyunsaturated fatty acids (PUFAs), particularly docosahexaenoic acid (DHA), an omega-3 (or n − 3) PUFA, but are also the main source of exposure to methylmercury (MeHg), a potent developmental neurotoxicant. Since n − 3 PUFAs support neural development and function, benefits deriving from a diet rich in n − 3s have been hypothesized to protect against deleterious effects of gestational MeHg exposure. To determine whether protection occurs at the behavioral level, female Long-Evans rats were exposed, in utero, to 0, 0.5, or 5 ppm of Hg as MeHg via drinking water, approximating exposures of 0, 40, and 400 μg Hg/kg/day and producing 0, 0.29, and 5.50 ppm of total Hg in the brains of siblings at birth. They also received pre- and postnatal exposure to one of two diets, both based on the AIN-93 semipurified formulation. A “fish-oil” diet was high in, and a “coconut-oil” diet was devoid of, DHA. Diets were approximately equal in α-linolenic acid and n − 6 PUFAs. As adults, the rats were first assessed with a spatial discrimination reversal (SDR) procedure and later with a visual (nonspatial) discrimination reversal (VDR) procedure. MeHg increased the number of errors to criterion for both SDR and VDR during the first reversal, but effects were smaller or non-existent on the original discrimination and on later reversals. No such MeHg-related deficits were seen when the rats were retested on SDR after 2 years of age. These results are consistent with previous reports and hypotheses that gestational MeHg exposure produces perseverative responding. No interactions between diet and MeHg were found, suggesting that n − 3 PUFAs do not guard against these behavioral effects. Brain Hg concentrations did not differ between the diets, either. In geriatric rats, failures to respond were less common and response latencies were shorter for rats fed the fish-oil diet, suggesting that exposure to a diet rich in n − 3s may lessen the impact of age-related declines in response initiation.
ISSN:0161-813X
1872-9711
DOI:10.1016/j.neuro.2007.05.001