The Role of PKA and Stress in Ethanol Sensitization

Univ Of North Carolina Chapel Hill, Chapel Hill NC

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Abstract

DESCRIPTION (provided by applicant): Previous research suggests that activation of the HPA axis leads to the development of behavioral sensitization to drugs of abuse. In addition, stress has been shown to reduced PKA function and RIIBeta (Rllp) expression in the frontal cortex of rats. The Rlbeta knockout (-/-) mouse model allows for the opportunity to study the effects of stress and ethanol in a model which has blunted PKA activity in several key brain regions. The Rllbeta subunit has been shown to be important in the protection against the development of behavioral sensitization: Rllbeta -/- mice are more susceptible to ethanol and amphetamine-induced locomotor sensitization. Experiement I will test the hypothesis that Rlbeta -/- mice are more susceptible to stress by evaluating several key aspects of HPA axis function before and after stressors. Experiment II will determine if stressors can substitute for ethanol in a sensitization paradigm. Finally, Experiment III will determine if antagonists of HPA axis signaling can block the acquisition and expression of locomotor sensitization. A better understanding of the role of stress in this model should broaden the field's understanding of the contributions of specific stressors to the development and maintenance of behavioral sensitization.