The Effects of Stimulant Drugs and Clonidine on Basal Ganglia Gene Expression

Grant Type
Grant Year
Institution Location
Institution Organization Name
University of Pennsylvania
Investigators Name
Mercugliano, Marianne, MD

Individuals with Tourette Syndrome often have Attention Deficit Hyperactivity Disorder (ADHD) which, in many cases, is their major hindrance to optimal functioning. While stimulant medications are dramatically effective for the treatment of symptoms associated with ADHD, they sometimes can exacerbate tics or induce them in susceptible individuals. In order to develop optimal pharmacologic treatments for children with ADHD and tics, an understanding of the neurophysiologic basis of stimulant-induced stereotypic motor behavior is imperative. The purpose of this study is to delineate changes in the expression of neurotransmitter-related genes in rats that occur during drug treatments which induce stereotypy in rats and tics in humans. The brain regions which will be studied include the midbrain dopamine neurons and the striatum, areas known to be affected by stimulant drugs and likely to be involved in the pathophysiology of stereotypy/ tics. The genes of interest include those encoding the main enzymes required for the synthesis of dopamine and GABA (two key neurotransmitters in these brain regions), the dopamine receptors which regulate dopamine’s effects in these two regions and specific neuropeptides which distinguish subgroups of striatal neurons projecting to different structures. Quantitative in situ hybridization is the method of choice for this study because it can be used to detect changes in the expression of individual genes in small groups of neurons within a structure. The effects of clinically relevant drugs which do (methylphenidate, dextro-amphetamine) and do not (clonidine) induce sterotypy/tics will be compared at different doses and regimens with concurrent behavioral studies to control for specificity of detected changes. The results of this study may provide information about the nature and location of changes in neurotransmission which occur with these drug treatments. Marianne Mercugliano, M.D. University of Pennsylvania, Philadelphia, PA Award $18,900 Tourette Association of America Inc. – Research Grant Award 1991