Implication of Striatal Dopamine D2 Receptors in Inhibitory Control and Habit Learning: A Tissue-Specific D2 Knockout Approach

Grant Type
Grant Year
Institution Location
Institution Organization Name
University of Chicago
Investigators Name
Cagniard, Barbara, PhD

Although the precise causes of TS are not yet determined, it has been theorized that tics are caused by either a hypersensitivity to or an increased number of dopamine D2 neurotransmitter receptors. Consistent with this, tics are known to be reduced by drugs that block dopamine D2 receptors (neuroleptics). Indeed, these medicines are the most commonly prescribed medication for treating tics. Unfortunately, neuroleptics also cause various short-term and long-term side effects. Because dopamine D2 receptors are expressed in many areas of the brain, it is critical to pinpoint the neuronal systems that specifically contribute to the development of the tics. In this way we can look toward the development of a more effective medication for TS treatment. Dopaminergic neurotransmission in the striatum; a subcortical structure, has been implicated in Tourette’s syndrome due to its importance in motor control and inhabitual or “automatic” behavioral responses such as tics. In this region of the brain dopamine D2 receptors are expressed by both dopamine and non-dopamine neurons. The dopamine neurons express both D2 “autoreceptors” that inhibit neuronal activity, while the non-dopamine neurons express D2 “heteroreceptors” that regulate dopaminergic output. Because neuroleptic drugs block both D2 autoreceptors and D2 heteroreceptors, the medicines we use do not enlighten us about the contribution of each receptor subpopulation and its role in causing TS symptoms. By comparing the data obtained at each different stage of a series of complex experiments, it will be possible to identify the specific contribution of D2 dopamine heteroreceptors in the development of tics. Thus, the current study will help to clarify the role of each specific subpopulation of D2 dopamine receptors in the neurobiology of tics and therefore will help the development of more effective medication for the treatment of Tourette’s syndrome. Barbara Cagniard, Ph.D., Depts. of Neurobiology, Pharmacology and Physiology, The University of Chicago, Chicago, IL Award: $40,000 Tourette Association of America Inc. – Research Grant Award 2003-2004