Effects of Cocaine on AMPA Receptor Phosphorylation in the Prefrontal Cortex of Mice Open Access
Curtin, Patrick Bryan (2015)
Abstract
Cocaine addiction is a serious and persistent problem in the United States. There is currently no FDA approved drug for the treatment of cocaine addiction and there is still much that is not understood about the changes the brain undergoes in response to cocaine. One of the newest areas of cocaine research focuses on cocaine's effect on glutamate and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. The goal of this study was to assess cocaine-induced changes in AMPA receptor phosphorylation using a sensitization model, which examines the locomotor activity of mice in response to repeated cocaine exposure. Although previous experiments have shown that AMPA receptor trafficking is sensitization-dependent, the effects of chronic cocaine exposure on serine 831 phosphorylation levels, a key phosphorylation site in the regulation of AMPA receptor trafficking, have not been investigated. Our goal was to compare the effects of acute and chronic cocaine administration on serine 831 phosphorylation. Locomotor activity was recorded every day for 5 days, and then again on a "challenge" day 3 days later, in 3 groups of C57BL/6 mice: one group (S/S) received saline every day, one group (S/C) received saline every day and then cocaine (15 mg/kg) on challenge day, and one group (C/C) received cocaine every day. Thirty min after the end of the challenge day session, animals were sacrificed and their prefrontal cortex and nucleus accumbens were collected and western blots of samples were performed. Cocaine increased locomotor activity in both the S/C and the C/C groups. However, contrary to what has previously been reported with this paradigm, we did not observe behavioral sensitization in the C/C group, defined as an increase in locomotor response over the days of cocaine treatment. Both the S/C and the C/C groups had similarly higher phosphorylation levels at serine 831 compared to the S/S control group, although the differences did not reach statistical significance. These results suggest that serine 831 phosphorylation is sensitive to acute and chronic cocaine exposure, and will help guide future experiments on cocaine-induced AMPA receptor changes.
Table of Contents
Introduction............................................................................1
Methods..................................................................................5
Results....................................................................................7
Discussion.............................................................................14
References.............................................................................18
About this Honors Thesis
| School | |
|---|---|
| Department | |
| Degree | |
| Submission | |
| Language |
|
| Research Field | |
| Keyword | |
| Committee Chair / Thesis Advisor | |
| Committee Members |
Primary PDF
| Thumbnail | Title | Date Uploaded | Actions |
|---|---|---|---|
|
|
Effects of Cocaine on AMPA Receptor Phosphorylation in the Prefrontal Cortex of Mice () | 2018-08-28 14:40:02 -0400 |
|
Supplemental Files
| Thumbnail | Title | Date Uploaded | Actions |
|---|