title: PPARγ agonism attenuates cocaine cue reactivity.
abstract: Cocaine use disorder is a chronic relapsing condition characterized by compulsive drug seeking and taking even after prolonged abstinence periods. Subsequent exposure to drug-associated cues can promote intense craving and lead to relapse in abstinent humans and rodent models. The responsiveness to these cocaine-related cues, or 'cue reactivity', can trigger relapse and cocaine-seeking behaviors; cue reactivity is measurable in cocaine-dependent humans as well as rodent models. Cue reactivity is thought to be predictive of cocaine craving and relapse. Here we report that PPARγ agonism during abstinence from cocaine self-administration reduced previously active lever pressing in Sprague Dawley rats during cue-reactivity tests, while administration of the PPARγ antagonist, GW9662, reversed this effect. PPARγ agonism also normalized nuclear ERK activity in the medial prefrontal cortex and hippocampus which was reversed with GW9662. Our results support the utility of PPARγ agonism as a relapse prevention strategy to maintain abstinence in the presence of cocaine-associated cues.
authors.affiliation: Department of Neurology, Galveston, TX, USA.|Center for Addiction Research, Galveston, TX, USA.|Mitchell Center for Neurodegenerative Diseases, Galveston, TX, USA.
authors.forename: William R
authors.initials: WR
authors.lastname: Miller
authors.affiliation: Center for Addiction Research, Galveston, TX, USA.|Department of Pharmacology and Toxicology, Galveston, TX, USA.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Fox
authors.affiliation: Center for Addiction Research, Galveston, TX, USA.|Department of Pharmacology and Toxicology, Galveston, TX, USA.
authors.forename: Sonja J
authors.initials: SJ
authors.lastname: Stutz
authors.affiliation: Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston, Houston, TX, USA.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Lane
authors.affiliation: Center for Addiction Research, Galveston, TX, USA.|Mitchell Center for Neurodegenerative Diseases, Galveston, TX, USA.|Division of Endocrinology, Internal Medicine University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Larry
authors.initials: L
authors.lastname: Denner
authors.affiliation: Center for Addiction Research, Galveston, TX, USA.|Mitchell Center for Neurodegenerative Diseases, Galveston, TX, USA.|Department of Pharmacology and Toxicology, Galveston, TX, USA.
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Cunningham
authors.affiliation: Department of Neurology, Galveston, TX, USA.|Center for Addiction Research, Galveston, TX, USA.|Mitchell Center for Neurodegenerative Diseases, Galveston, TX, USA.
authors.forename: Kelly T
authors.initials: KT
authors.lastname: Dineley
mesh_terms: D000813:Anilides / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders; D066249:Craving / Q000187:drug effects; D003463:Cues; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D058999:Drug-Seeking Behavior / Q000187:drug effects*; D008124:Locomotion / Q000187:drug effects; D020935:MAP Kinase Signaling System; D047495:PPAR gamma / Q000819:agonists* / Q000037:antagonists & inhibitors*; D000077205:Pioglitazone / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012008:Recurrence; D012646:Self Administration
chemical_list: C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D018765:Dopamine Uptake Inhibitors; D047495:PPAR gamma; D003042:Cocaine; D000077205:Pioglitazone
keywords: ERK MAPK; hippocampus; pioglitazone; prefrontal cortex; relapse prevention