title: The phosphodiesterase inhibitor isobutylmethylxanthine attenuates behavioral sensitization to cocaine.
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.
authors.affiliation: Department of Psychology, Behavioral Neuroscience Program, Connecticut College, New London, Connecticut 06320, USA. jasch@conncoll.edu
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Schroeder
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Ruta
authors.forename: Jessica S
authors.initials: JS
authors.lastname: Gordon
authors.forename: Andrea S
authors.initials: AS
authors.lastname: Rodrigues
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Foote
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology*; D000241:Adenosine / Q000096:biosynthesis; D000818:Animals; D016739:Behavior, Addictive; D001522:Behavior, Animal / Q000187:drug effects*; D003042:Cocaine / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D010726:Phosphodiesterase Inhibitors; D000242:Cyclic AMP; D003042:Cocaine; D000241:Adenosine; D015056:1-Methyl-3-isobutylxanthine