A growing body of evidence suggests that inadequate incorporation of docosahexaenoic acid (DHA) in brain during development affects the CNS dopamine systems and, when combined with appropriate genetic and/or other epigenetic factors, contribute to the risk of developing ADHD or to the severity of the disease. This proposal addresses the HYPOTHESIS that low brain DHA levels during early development alter dopaminergic function producing hyperactivity and attentional deficits similar to the symptoms of ADHD. The OBJECTIVE of this study is to assess the behavioral and neurochemical effects of clinically-relevant variation in brain DHA content during early development.
The Specific Aims will use a rat model to determine: ? ? 1. The effects of low brain DHA content during early development on activity and attentional processes in the developing rat. A force-plate actometer will be used to measure simultaneously assess activity and attentional processes in rats raised from conception on diets designed to modulate brain DHA content. ? ? 2. The effects of methylphenidate on hyperactivity and attentional processes in juvenile rats with low brain DHA content during early development. Dose-response effects of this drug used in the treatment of ADHD will be determined using the force-plate actometer. ? ? 3. The effects of low brain DHA content during early development on dopaminergic neurochemistry in juvenile rats. Dopamine content and turnover and the density of dopamine receptors and transporters will be assessed in specific brain regions. ? ? 4. The critical developmental period(s) when sufficient brain DHA content is essential for normal development of the dopamine systems. Treatment with DHA will be initiated at various time points between birth and weaning to determine when neuroplasticity is present. ? ? These experiments will show the relationship between brain DHA content and dopaminergic functioning and behavioral indices of hyperactivity and attentional processes. These findings will provide timely and important insights into mechanisms of brain development and perinatal nutrition and provide insights into the etiology of ADHD in humans. Such insights may identify a means by which certain risk factors for ADHD may be reduced or eliminated or the severity of the disease may be reduced through appropriate pre- and postnatal nutrition. ? ?

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
Project #
Application #
Study Section
Developmental Brain Disorders Study Section (DBD)
Program Officer
Winsky, Lois M
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Kansas
Schools of Medicine
Kansas City
United States
Zip Code
Levant, Beth; Zarcone, Troy J; Davis, Paul F et al. (2011) Differences in methylphenidate dose response between periadolescent and adult rats in the familiar arena-novel alcove task. J Pharmacol Exp Ther 337:83-91
Levant, Beth; Zarcone, Troy J; Fowler, Stephen C (2010) Developmental effects of dietary n-3 fatty acids on activity and response to novelty. Physiol Behav 101:176-83
Fowler, Stephen C; Zarcone, Troy J; Levant, Beth (2010) Methylphenidate attenuates rats' preference for a novel spatial stimulus introduced into a familiar environment: assessment using a force-plate actometer. J Neurosci Methods 189:36-43
Ahmad, S Omar; Park, Ji-Hyuk; Radel, Jeffery D et al. (2008) Reduced numbers of dopamine neurons in the substantia nigra pars compacta and ventral tegmental area of rats fed an n-3 polyunsaturated fatty acid-deficient diet: a stereological study. Neurosci Lett 438:303-7
Richards, Toni L; Pazdernik, Thomas L; Levant, Beth (2007) Clorgyline-induced modification of behavioral sensitization to quinpirole: effects on local cerebral glucose utilization. Brain Res 1160:124-33
Richards, Toni L; Pazdernik, Thomas L; Levant, Beth (2007) Basal local cerebral glucose utilization is not altered after behavioral sensitization to quinpirole. Neurosci Lett 429:165-8
Levant, Beth; Ozias, Marlies K; Jones, Karra A et al. (2006) Differential effects of modulation of docosahexaenoic acid content during development in specific regions of rat brain. Lipids 41:407-14
Levant, Beth; Ozias, Marlies K; Carlson, Susan E (2006) Sex-specific effects of brain LC-PUFA composition on locomotor activity in rats. Physiol Behav 89:196-204
Levant, Beth; Crane, Jennifer F; Carlson, Susan E (2006) Sub-chronic antipsychotic drug treatment does not alter brain phospholipid fatty acid composition in rats. Prog Neuropsychopharmacol Biol Psychiatry 30:728-32