How and Where Methylphenidate Exerts Effect in Adolescent and Adult Brains

University Of Texas Hlth Sci Ctr Houston, Houston TX

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Abstract

DESCRIPTION (provided by applicant): Recent publication in the November 2006 edition of the Journal of the American Academy of child and adolescent Psychiatry report the risks and benefits of methylphenidate (MPD) use in the treatment of attention deficit hyperactive disorder (ADHD) and strongly indicate the need of basic science research of MPD. The majority of the MPD investigations studied the drug effects on animal behavior using behavioral assays before and after different means of drug administration and lesioning as well as neurochemical and molecular approaches. MPD exerts its effect on the brain, therefore one of the best approaches to study the physiology and the MPD mechanism of action is to record the neurophysiological events from the brain itself. There are limited in vivo or in vitro neurophysiological reports that study the effect of MPD on one selective brain area. At the present, there is not one report to our knowledge that records the neuronal activity from several brain sites simultaneously in adolescent and adult freely behaving animals previously implanted stereotaxical with permanent electrodes as well as recording from the same animals their behavior using dose response protocol. The objective of this proposal is: 1) to obtain the functional neuronal circuit of MPD action; 2) to obtain the window (latency and duration) of MPD action in each of the 5 structures proposed for each dose; 3) to obtain the neurophysiological activity underlying MPD administration using dose response protocol; and 4) to determine behaviorally and neurophysiologically the dose response characteristics of MPD in MPD naive adolescent and adult animals and in animals treated chronically with the drug . The general hypothesis of this study is that MPD elicited down regulation in 4 brain site(s), and up-regulation in one brain site(s). The aim of this study is to verify this hypothesis. The result from this proposal will provide the functional circuit and the property of MPD action, and the vital mechanism underlying MPD therapy.