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The Effects of Cocaine Self-Administration on Cognition and Brain Metabolism

Porter, Jessica (2012) The Effects of Cocaine Self-Administration on Cognition and Brain Metabolism. Doctoral Dissertation, University of Pittsburgh.

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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: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Porter, Jessicadrjnp13@gmail.com
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairSved, Alan Fsved@pitt.eduSVED
Thesis AdvisorBradberry, Charlesbradberrycw@umpc.edu
Committee MemberDonny, Ericedonny@pitt.eduEDONNY
Committee MemberPrice, Juliepricjc@upmc.edu
Committee MemberLuna, Beatrizlunab@upmc.eduLUNA
Committee MemberGaravan, Hughhgaravan@uvm.edu
Date: 13 December 2012
Date Type: Publication
Defense Date: 28 November 2012
Approval Date: 13 December 2012
Submission Date: 10 December 2012
Release Date: 13 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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