Degree Name

PhD (Doctor of Philosophy)

Program

Biomedical Sciences

Date of Award

12-2009

Committee Chair or Co-Chairs

Russell W. Brown

Committee Members

Ronald H. Baisden, Richard M. Kostrzewa, Kenneth E. Ferslew, Donald B. Hoover

Abstract

In past work, we have shown neonatal quinpirole (dopamine D2/D3 agonist) treatment produces a significant increase in dopamine D2 receptor sensitivity, a phenomenon known as D2 receptor priming. Dopamine D2 receptor priming is common in psychosis. Male and female rats were administered quinpirole (1mg/kg) or saline from postnatal days 1-11 and raised to adulthood (P60). As adults, rats were administered d-amphetamine sulfate (1mg/kg) or saline every other day for 14 days. Approximately 10 min before each amphetamine or saline injection, animals were administered the D1 antagonist SCH 23390 (0.1 mg/kg), the D2 antagonist eticlopride (0.1 mg/kg) or saline. After both injections, rats were placed in a locomotor arena and activity was analyzed for a 10-min period. Results indicated that D2-priming enhanced locomotor activation effects to amphetamine in both males and females, with females demonstrating higher levels of behavioral activation. SCH 23390 blocked amphetamine sensitization in both males and females to levels below saline controls, whereas eticlopride was more effective in blocking amphetamine sensitization in males as compared to females, although eticlopride did block elevations of behavioral activation in D2-primed males and females. Seven to 10 days after sensitization, microdialysis was performed and amphetamine produced a five-fold increase in dopamine overflow in the nucleus accumbens compared to non D2-primed rats administered amphetamine. Both D1 and D2 antagonism were effective at blocking amphetamine-induced increases in dopamine overflow. These results show that neonatal quinpirole treatment enhances behavioral activation and dopamine overflow, but there appear to be sex differences in the D2 as compared to D1 response to behavioral activation produced by amphetamine.

Document Type

Dissertation - Open Access

Copyright

Copyright by the authors.

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