Neural Mechanisms of Sensitization-induced Tic-like movements (2nd year)

Grant Type
Basic
Grant Year
2008-2009
Institution Location
MI
Institution Organization Name
University of Michigan
Investigators Name
Aldridge, J. Wayne, PhD

Motor tics are a major problem in Tourette Syndrome, and while we do not know what goes wrong in the brain to cause tics, we do suspect that there is a malfunction in the regulation of the neurotransmitter (brain chemical) dopamine. This change disrupts normal cell activity in the basal ganglia, a group of brain structures involved in movement control. The goal of this project is to determine how dopamine in the basal ganglia regulates and organizes movements. To accomplish this goal, we test the effect of drugs that act upon dopamine receptors. The system we use to study movements is grooming behavior in rodents. Grooming consists of a variety of movements, some of which occur in highly organized sequences. As part of our 2007 TSA award we found that rats given a drug to increase D1 receptors performed more tic-like scratching and biting behaviors when compared to normal rats. In the present study we will examine another dopamine receptor, the D2 receptor, which is also important for repetitive scratching and biting. Haloperidol is used to treat tics in some people with TS. We will test the hypothesis that haloperidol, a drug that blocks D2 receptors, will diminish the ability of D1 receptors to increase scratching and biting. Prevention of these behaviors by haloperidol would support the notion that our grooming model is a useful way to study the brain mechanisms underlying tics. Using this model system, we will also study brain mechanisms directly that are in a part of the basal ganglia called the substantia nigra pars reticulata. We will implant electrodes and record the activity of single neurons during scratching and biting behavior of normal rats and rats with increased D1 receptors. We anticipate that the number of neurons activated will be related to the amount of scratching and biting. In these animals that are producing excess tic-like scratching and biting, we expect to observe more neural activation. Together, these studies should broaden our knowledge of how dopamine regulates the repetition of motor actions. We believe that these findings may help us understand how tics are generated in the brain. J. Wayne Aldridge, Ph.D., Jennifer Taylor, Ph.D. University of Michigan Medical School, Ann Arbor, MI Award: $72,453 (2nd Year) Tourette Association of America Inc. – Research Grant Award 2008-2009