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

2005 2005

Other formats: Order a copy

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)

0317: Neurology
Identifier / keyword
Biological sciences; CREB; Reinstatement; Reward; Stress
The role of cAMP response element binding (CREB) protein in mediating stress induced reward and reinstatement
Kreibich, Arati Sadalge
Number of pages
Publication year
Degree date
School code
DAI-B 66/12, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
0542435209, 9780542435201
Blendy, Julie
University of Pennsylvania
University location
United States -- Pennsylvania
Source type
Dissertations & Theses
Document type
Dissertation/thesis number
ProQuest document ID
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
Access the complete full text

You can get the full text of this document if it is part of your institution's ProQuest subscription.

Try one of the following:

  • Connect to ProQuest through your library network and search for the document from there.
  • Request the document from your library.
  • Go to the ProQuest login page and enter a ProQuest or My Research username / password.