The Effect of Mild Copper Deficiency on Fear Extinction and Motor Functioning




Lippi, Stephen Lawrence Patrick

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Biometals play a large role within the human body where a deviation from normal levels can result in behavioral abnormalities. Copper (Cu) is a transition metal with physiological importance and has been shown to have a remediating effect on the behavioral impairments caused by excess Zinc (Zn). In order to examine the effects of a Cu deficient diet directly, diets mildly deficient in Cu with identical Zn levels were developed and resulting behavioral effects were examined. Forty-five male Sprague- Dawley rats were tested for cued fear learning, fear extinction, and motor functioning in order to assess the effect of dietary metal content on behavior. Using specially formulated diets, a mild Cu deficiency was examined directly, as opposed to a Cu deficiency attained through excess levels of Zn. Animals were given a Cu deficient diet (4ppm Cu) while still in prenatal development, a Cu deficient diet (4ppm) after birth (postnatal), and a Cu control diet (16ppm) after birth (postnatal) and were raised for a period of 4 months. Throughout the fear learning and extinction paradigm, there were no significant differences between the dietary conditions except on the second day of fear extinction recall where a marginally significant difference was detected with the prenatal Cu deficient group exhibiting higher percent freezing than the postnatal Cu deficient and control groups. However, in analysis of the accelerating rotarod task, significant differences between the diets were found on days 2 and 3 as well as when the performance was averaged across all three days of testing and across the nine total trials. The postnatal Cu deficient group consistently exhibited lower latencies to fall. Significant differences were noted in the weights between the dietary groups. At weaning (PND 21), the prenatal Cu deficient weighed significantly more than the postnatal Cu deficient, and at 4 months of age, the postnatal Cu control group weighed significantly more than the pre- and postnatal Cu deficient groups. These results suggest that a diet mildly deficient in Cu may lead to motor abnormalities and impairment and not necessarily lead to significant differences in fear learning. These data show the important role that dietary metal content plays in behavior and that using appropriate control and experimental diets can have a significant effect on rodent behavioral experiments.



Copper, Fear extinction, Deficiency, Zinc, Nutrition, Biometals