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Updated: May 23, 2026

Assessment of Cocaine-induced Behavioral Sensitization and Conditioned Place Preference in Mice
Published on: February 18, 2016
The phosphodiesterase inhibitor isobutylmethylxanthine attenuates behavioral sensitization to cocaine
Joseph A Schroeder1, Jeffrey D Ruta, Jessica S Gordon
1Department of Psychology, Behavioral Neuroscience Program, Connecticut College, New London, Connecticut 06320, USA. jasch@conncoll.edu
Abstract:
The factors influencing sensitization to cocaine are complex and likely include both cellular and neural systems factors. Upregulation of the striatal dopamine cAMP-signaling pathway and enhanced accumbens adenosine tone are two mechanisms that have been proposed to underlie the development of cocaine sensitization. Isobutylmethylxanthine (IBMX) is a nonspecific inhibitor of phosphodiesterase (PDE) that may enhance the intracellular cAMP levels. However, IBMX may inhibit the PDE-mediated production of adenosine. In this study, intracerebroventricular IBMX did not affect the acute hyperlocomotor response to cocaine, but when coadministered with cocaine for 7 consecutive days, attenuated development of behavioral sensitization. These results suggest that IBMX inhibition of PDE-mediated adenosine production is a stronger influence on cocaine sensitization than inhibition of intracellular PDE-mediated cAMP metabolism.
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