Studies on the Co-Expression of Dopamine D2 Receptor mRNA’s Neuropeptide and Transmitter Related mRNA’s in the Basal Ganglia

Grant Type
Grant Year
Institution Location
Institution Organization Name
Institute of Animal Physiology & Genetics Research England
Investigators Name
Augood, Sarah, BSC

Due to the undoubted efficacy of dopamine antagonists (such as haloperidol) in ameliorating the symptoms of Tourette Syndrome (TS), it is now thought that the basal ganglia nuclei may hold the key to discovering the etiology of this movement disorder. Of particular interest amongst this collection of anatomical nuclei, is the caudate-putamen (striatum) which is particularly enriched in dopamine receptor binding sites. It is my intention to attempt to unravel some of the neurochemical complexities of the basal ganglia by selectively identifying which neuropeptide and neurotransmitter messenger RNA’s (mRNA’s) are co-expressed with dopamine D2 receptor mRNA’s in human and rat striatal cells using the combined techniques of radioactive and non radioactive in situ hybridization. This type of detailed analysis of the chemical circuitary of the striatum is likely to be fundamental to the understanding of human basal ganglia function as our earlier studies of primate and rat striatal tissue indicate that a complex cascade of changes in gene expression occurs following dopamine D2 receptor blockade (with drugs such as haloperidol). It is these post synaptic changes which are likely to be involved in the development of some of the side effects of neuroleptic treatment found in TS patients. By investigating which neuropeptide/neurotransmitter mRNA containing striatal cells also express the dopamine D2 mRNA’s, I will be able to study further, at the cellular level, how neuroleptic treatment modulates the expression of co-expressed neuropeptide mRNA’s such as enkephalin, dynorphin, substance P and neurotensin in addition to the effect D2 receptor blockade has on GABA mRNA — the major inhibitory neurotransmitter contained within many striatal cells. The advantage of this approach is that it allows the cellular localization of two different mRNA’s to be detected within the same tissue section or indeed within the same cell. It is our hope that knowledge of the regulation and co-expression of neuropeptide mRNA’s with the D2 receptor mRNA’s in striatal cells will enable us to begin to understand when, where and how neuroleptics produce their effects at the cellular level. Sarah Jane Augood, BSc. Institute of Animal Physiology & Genetics Research, Babraham, Cambridge, England Award $25,000 Tourette Association of America Inc. – Research Grant Award 1990