Localization and Regulation of cAMP Phosphodiesterases in Dopamine Receptor-Expressing Neurons and the Possible Relevance for Tourette Syndrome

Grant Type
Grant Year
Institution Location
Institution Organization Name
Boston University
Investigators Name
Cherry, James, PhD

The physiological bases and the neuroanatomical loci that cause Tourette Syndrome (TS) remain unknown. On one hand, the effec-tiveness of dopamine receptor antagonists such as haloperidol in alleviating some TS symptoms provides strong evidence for the involvement of dopaminergic pathways in TS pathology. On the other hand, abnormalities in many other neurotransmitter systems throughout the brain have also been hypothesized to underlie TS. In an attempt to unify these different findings, Singer et al (1990) proposed that defects in second messenger metabolism might represent a potentially common mechanism for this widespread neurotransmitter dysfunction in TS. Unfortunately, formal tests of this hypothesis have been lacking. We have proposed to address this issue by looking more closely at the distribution of certain enzymes which regulate levels of the second messenger cAMP in neurons. These studies may help to identify novel pathways by which haloperidol and other classical neuroleptic drugs act in the nervous system. Although effective in suppressing motor and phonic tics in TS patients, side effects caused by these agents limit their usefulness as long-term therapies. Data obtained from our studies will hopefully point to new targets for future drug design and therapeutic interventions. James A. Cherry, Ph.D. Boston University, Boston, MA Award: $32,744 Tourette Association of America Inc. – Research Grant Award 1997