Abstract/Details

The role of cAMP response element binding (CREB) protein in mediating stress induced reward and reinstatement


2005 2005

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Abstract (summary)

Exposure to stress can increase initial drug-taking as well as relapse to drug use. In this thesis, we have shown that repeated forced swim (FS) exposure prior to initial drug exposure can augment stress induced acquisition of cocaine conditioned place preference (CPP) in wild type mice. In addition, stress can precipitate previously extinguished CPP. We have further shown that an acute exposure to FS, in a context distinct from conditioning, induces reinstatement of cocaine CPP in wild type mice.

To determine if this change in cocaine reward and reinstatement is dependent on CREB, we examined the behavior of mice deficient in α and Δ isoforms of CREB in these paradigms. The CREBαΔ mutant mice show deficits in FS induced enhancement as well as reinstatement of cocaine conditioned place preference. In contrast, they show robust cocaine induced reinstatement.

The CRF1 receptor mediates responses to stress as well as to drugs of abuse. To investigate if changes in CRF1 receptor signaling can affect these stress induced changes in behavior in a CREB dependent manner, we examined the role of CRF1 receptor blockade in these paradigms. We find that antalarmin administration attenuates stress-induced potentiation of cocaine reward as well as FS induced reinstatement of place preference. In addition, antalarmin pretreatment blocks pCREB activation during cocaine conditioning and after FS induced reinstatement in the amygdala. This implies that the CRF1 receptor may act upstream of CREB signaling in mediating FS induced reinstatement of cocaine CPP.

Together, these data reveal the common receptor signaling and molecular mechanisms underlying behavioral effects that may affect both initial drug taking as well as relapse to addiction. Exploring pharmacotherapies based on these data may provide viable options for treatment of cocaine addiction in the future.

Indexing (details)


Subject
Neurology
Classification
0317: Neurology
Identifier / keyword
Biological sciences; CREB; Reinstatement; Reward; Stress
Title
The role of cAMP response element binding (CREB) protein in mediating stress induced reward and reinstatement
Author
Kreibich, Arati Sadalge
Number of pages
238
Publication year
2005
Degree date
2005
School code
0175
Source
DAI-B 66/12, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
ISBN
0542435209, 9780542435201
Advisor
Blendy, Julie
University/institution
University of Pennsylvania
University location
United States -- Pennsylvania
Degree
Ph.D.
Source type
Dissertations & Theses
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
3197697
ProQuest document ID
305443673
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
http://search.proquest.com/docview/305443673
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