High dietary alpha tocopherol improves attention deficit/hyperactivity (ADHD)‐like behavior in juvenile spontaneously hypertensive rats (SHR)

Abstract

The juvenile SHR, a widely used animal model for ADHD, was previously shown to have low levels of alpha tocopherol (AT) in plasma and brain compared to Sprague-Dawley (SD) rats on the same diet. In this study we asked if AT levels are related to the behavior abnormalities associated with ADHD (inattention, hyperactivity, and impulsivity), using measures previously shown to distinguish these behaviors. Because AT might affect behavior by protection of important brain PUFAs such as arachidonic and docosahexaenoic acids (AA and DHA), fatty acid analysis was also done. Three groups of SHR (n=8 each) were fed synthetic AIN93 diets containing, respectively, 0, 50 and 250 U/kg AT acetate, and 8 SD rats were given the 50 U/kg AT diet. The diets were fed ad libitum from the age of 4 weeks. Behavior testing was done from 8 weeks to 12 weeks in conditioning cages equipped with infrared monitors. The animals were killed at 12 weeks. AT concentrations in plasma of SHRs increased with increasing dietary AT (1.47 ± 0.64, 56.3 ± 6.39, 69.4 ± 12.8 μM), approaching that of SDs (71.0 ± 12.1 μM). AT concentrations in brain followed a similar pattern (5.49 ± 0.54, 14.5 ± 0.69, 17.2 ± 1.06 μg/g compared to 18.6 ± 2.00 μg/g). Total n-3 PUFA in SHR plasma and the AA + DHA sum in SHR brain also increased in response to dietary AT. SHR behavior showed significant effects of dietary treatment. Measures of learning (attention), inhibition, and impulsivity improved with increasing AT. Total activity was not reduced by AT. Replenishment of AT in the SHR can improve behavior. Supported by the Purdue Research Foundation.