The role of 5-HT2c Receptors in controlling Basal Ganglia Putput in the Rat: Revelance for Motor and Attentional Disturbances in Tourette Syndrome

Grant Type
Basic
Grant Year
2003-2004
Institution Location
Institution Organization Name
Istituto di Richerche Italy
Investigators Name
Esposito, Ennio, PhD

A complex neurobiological disorder that emerges in childhood, Tourette Syndrome (TS) is frequently associated with attention deficit hyperactivity disorder (ADHD), obsessive compulsive disorder (OCD), poor impulse control, and other coexisting behavioral manifestations. Although the exact neuroanatomic location of TS remains unknown; it is believed that the condition involves dysfunction in multiple brain systems that affect neural transmission of the motor circuit of the basal ganglia. Recent PET studies as well as postmortem measurements suggest that changes in dopaminergic and serotonergic neurotransmission may be involved in TS. Decreased levels of homovanillic acid (a dopaminergic metatabolite) were found in the cerebrospinal fluid of TS patients. Postmortem studies of brains from TS individuals showed lower concentrations of serotonin (5-HT) and 5-hydroxyindoleacetic acid, a major metabolite of serotonin. These findings may account for the therapeutic effect attained by manipulating these neurotransmitters. Furthermore, converging lines of evidence suggest that dysfunction of brain serotonergic systems, either directly or indirectly, predisposes people to impulsive behavior. With a view toward learning more about their interactions, we will be focusing on several brain functions suspected of being involved with causing TS symptoms – both motor and behavioral. Intriguing recent findings about brain receptors in two specific brain regions provide the potential for improved understanding of new and hopefully useful pharmacological treatments. Ennio Esposito M.D., Ph.D., Laboratory of Neurophysiology Istituto di Ricerche Farmacologiche Mario Negri, Chieti, Italy Award: $75,000 Tourette Association of America Inc. – Research Grant Award 2003-2004