title: Transforming growth factor beta receptor 1 is increased following abstinence from cocaine self-administration, but not cocaine sensitization.
abstract: The addicted phenotype is characterized as a long-lasting, chronically relapsing disorder that persists following long periods of abstinence, suggesting that the underlying molecular changes are stable and endure for long periods even in the absence of drug. Here, we investigated Transforming Growth Factor-Beta Type I receptor (TGF-β R1) expression in the nucleus accumbens (NAc) following periods of withdrawal from cocaine self-administration (SA) and a sensitizing regimen of non-contingent cocaine. Rats were exposed to either (i) repeated systemic injections (cocaine or saline), or (ii) self-administration (cocaine or saline) and underwent a period of forced abstinence (either 1 or 7 days of drug cessation). Withdrawal from cocaine self-administration resulted in an increase in TGF-β R1 protein expression in the NAc compared to saline controls. This increase was specific for volitional cocaine intake as no change in expression was observed following a sensitizing regimen of experimenter-administered cocaine. These findings implicate TGF-β signaling as a novel potential therapeutic target for treating drug addiction.
authors.affiliation: Department of Pharmacology & Toxicology, University at Buffalo, Buffalo, New York, United States of America ; Research Institute on Addictions, University at Buffalo, Buffalo, New York, United States of America.
authors.forename: Amy M
authors.initials: AM
authors.lastname: Gancarz-Kausch
authors.affiliation: Department of Pharmacology & Toxicology, University at Buffalo, Buffalo, New York, United States of America.
authors.forename: Gabrielle L
authors.initials: GL
authors.lastname: Schroeder
authors.affiliation: Department of Pharmacology & Toxicology, University at Buffalo, Buffalo, New York, United States of America.
authors.forename: Clarisse
authors.initials: C
authors.lastname: Panganiban
authors.affiliation: Department of Pharmacology & Toxicology, University at Buffalo, Buffalo, New York, United States of America.
authors.forename: Danielle
authors.initials: D
authors.lastname: Adank
authors.affiliation: Department of Pharmacology & Toxicology, University at Buffalo, Buffalo, New York, United States of America.
authors.forename: Monica S
authors.initials: MS
authors.lastname: Humby
authors.affiliation: Department of Pharmacology & Toxicology, University at Buffalo, Buffalo, New York, United States of America.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Kausch
authors.affiliation: Department of Pharmacology & Toxicology, University at Buffalo, Buffalo, New York, United States of America ; Research Institute on Addictions, University at Buffalo, Buffalo, New York, United States of America.
authors.forename: Stewart D
authors.initials: SD
authors.lastname: Clark
authors.affiliation: Department of Pharmacology & Toxicology, University at Buffalo, Buffalo, New York, United States of America ; Research Institute on Addictions, University at Buffalo, Buffalo, New York, United States of America.
authors.forename: David M
authors.initials: DM
authors.lastname: Dietz
mesh_terms: D000818:Animals; D003042:Cocaine / Q000008:administration & dosage* / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D012646:Self Administration; D015398:Signal Transduction / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625843:Tgfbr1 protein, rat; D003042:Cocaine