Author

Garimella

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.

Included in

Biology Commons

Share

COinS