Molecular Biology Studies of Historically Neglected Central D2 Dopamine Receptors

Grant Type
Clinical
Grant Year
1990
Institution Location
FL
Institution Organization Name
University of Florida
Investigators Name
MacLennan, A. John, PhD

D2 dopamine (DA) receptors located somewhere in the brain are likely the primary site of action for most currently employed pharmacological treatments of Tourette Syndrome (TS). Furthermore, data suggests that TS results from an abnormally high concentration of brain D2 DA receptors. D2 DA receptors are present in many brain regions which serve separate functions. Research has yet to establish which D2 DA receptors are involved in the cause or treatment of TS. The vast majority of research investigating D2 DA receptors has dealt with only those receptors located in either the pituitary or regions of the nigrostriatal and mesolimbic DA systems. Therefore, the potentially important, but neglected, D2 receptors found in many other areas of the brain deserve more attention. The characterization and comparison of neurons that contain D2 receptors may lead to new treatments that are capable of reducing the symptoms of TS, but are less likely to elicit the frequent and debilitating side effects presently observed. We have chosen to examine neurons in the oculomotor nucleus, pons and medulla which express mRNA that contains the genetic information used by these cells to synthesize D2 receptors (i.e., D2 mRNA). We have selected these brain regions for three primary reasons. First, D2 receptors in these regions have definitely been neglected. Second, the population of D2 mRNA’s in the pons and medulla is distinguishable from that found in the pituitary and the mesolimbic and nigrostriatal DA systems. Third, the oculomotor nucleus and many regions of the pons and medulla are involved in the control of muscle groups which are affected by TS. We will use an in situ hybridization histochemistry method to identify neurons that contain D2 mRNA. Immunohistochemistry will then be combined with the in situ hybridization to determine which neurotransmitter systems are utilized by the D2 mRNA-containing neurons. Finally retrograde tracing techniques will be employed to reveal which other brain regions are affected by these neurons. A. John MacLennan, Ph.D. University of Florida, Gainesville, FL Award $25,000 Tourette Association of America Inc. – Research Grant Award 1990