Porter, Jessica
(2012)
The Effects of Cocaine Self-Administration on Cognition and Brain Metabolism.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Cocaine users display a wide range of cognitive impairments and dysfunction in brain regions important for cognition. Treatment outcome is dependent on cognitive ability. It is important to understand these deficits and the underlying neurobiology. The first aim was to determine whether cocaine is sufficient to cause cognitive deficits, and if so, to determine the specificity of these cognitive deficits. Secondly, we assessed cerebral metabolic function after a drug free period. We used rhesus monkeys in a longitudinal study in which 14 animals were characterized prior to assignment to matched control (n=6) and cocaine self-administration (n=8) groups. Self-administration took place daily over nine months during which, visual and auditory contextual cues were presented. Weekly cognitive assessments were conducted following a 72 hour drug free period. We employed a stimulus discrimination/reversal task to evaluate associative learning and cognitive flexibility and the delayed match-to-sample task to assess visual working memory. In the cocaine group, we observed significant impairments in reversal performance and visual working memory after self-administration compared to controls. We examined distractibility in both groups, using brief novel distractors. Subsequently, an identical approach was used for exposure to a distractor previously associated with cocaine (experimental group), or water in the control group. In the cocaine group, stimulus discrimination was unaffected by either distractor, whereas reversal performance was disrupted by both the novel and appetitive distractors relative to baseline. Visual working memory was impaired in the cocaine group in the presence of the novel distractor. The control group’s performance was unaffected by the presentation of either distractor. Monkeys were drug free for 20 months prior to assessment of metabolic function using 18F-2-deoxyfluoro-D-glucose positron emission tomography. The cocaine group showed greater cerebellar activity than the control group while performing a visual working memory task (relative to control task). This work confirms that cocaine self-administration is sufficient to cause long lasting cognitive impairments in cognitive control, visual working memory and attention. These data also suggest that cocaine exposure alters cerebellar function, but future studies will need to be conducted to confirm that cocaine exposure is the direct cause of the metabolic differences observed.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
13 December 2012 |
| Date Type: |
Publication |
| Defense Date: |
28 November 2012 |
| Approval Date: |
13 December 2012 |
| Submission Date: |
10 December 2012 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
119 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Medicine > Neurobiology |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
addiction, executive function, imaging, cocaine, cognition |
| Date Deposited: |
13 Dec 2012 20:11 |
| Last Modified: |
19 Dec 2016 14:40 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/16881 |
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