Date of Award
12-2000
Degree Name
Master of Science
Department
Biological Sciences
First Advisor
Dr. Kalpana Merchant
Second Advisor
Dr. Karim Essani
Third Advisor
Dr. Leonard Beuving
Fourth Advisor
Dr. Robert Eisenberg
Access Setting
Masters Thesis-Open Access
Abstract
The role of dopamine D4 receptors in the induction and expression of behavioral sensitization to amphetamine, cocaine and PCP was investigated in this study. Behavioral changes and genomic responses accompanying sensitization were examined using a highly selective D4 receptor antagonist, PNU-101387G. Induction and expression of behavioral sensitization to cocaine was blocked by PNU-101387G. However, the D4 antagonist did not modulate the induction and expression of behavioral sensitization to PCP. Neuroadaptive genomic responses accompanying acute and chronic effects of amphetamine and their modulation by PNU-101387G was examined by looking at alterations in the expression of two immediate-early genes: c-fos and NGFI-A. The D4 antagonist did not alter amphetamine-induced . NGFI-A expression at 0.1 mg/kg or 1 mg/kg, but attenuated NGFI-A mRNA levels at 10 mg/kg. The 4-day pretreatment paradigm to examine the role of PNU-101387G in the development of sensitization did not produce behavioral sensitization in response to an amphetamine challenge on day 5. In addition, c-fos mRNA induction was not attenuated significantly in these rats suggesting a dependence of some genomic changes on withdrawal-induced neuroplasticity. Taken together, these data suggest a prominent role for the D4 receptors in the development and expression of behavioral sensitization to amphetamine and cocaine but not PCP.
Recommended Citation
Garimella, Bina, "Role of Dopamine D4 Receptor in the Genomic and Behavioral Effects of Psychostimulants: Relevance to Schizophrenia" (2000). Masters Theses. 4694.
https://scholarworks.wmich.edu/masters_theses/4694