title: Blocking Infralimbic Basic Fibroblast Growth Factor (bFGF or FGF2) Facilitates Extinction of Drug Seeking After Cocaine Self-Administration.
abstract: Drug exposure results in structural and functional changes in brain regions that regulate reward and these changes may underlie the persistence of compulsive drug seeking and relapse. Neurotrophic factors, such as basic fibroblast growth factor (bFGF or FGF2), are necessary for neuronal survival, growth, and differentiation, and may contribute to these drug-induced changes. Following cocaine exposure, bFGF is increased in addiction-related brain regions, including the infralimbic medial prefrontal cortex (IL-mPFC). The IL-mPFC is necessary for extinction, but whether drug-induced overexpression of bFGF in this region affects extinction of drug seeking is unknown. Thus, we determined whether blocking bFGF in IL-mPFC would facilitate extinction following cocaine self-administration. Rats were trained to lever press for intravenous infusions of cocaine before extinction. Blocking bFGF in IL-mPFC before four extinction sessions resulted in facilitated extinction. In contrast, blocking bFGF alone was not sufficient to facilitate extinction, as blocking bFGF and returning rats to their home cage had no effect on subsequent extinction. Furthermore, bFGF protein expression increased in IL-mPFC following cocaine self-administration, an effect reversed by extinction. These results suggest that cocaine-induced overexpression of bFGF inhibits extinction, as blocking bFGF during extinction permits rapid extinction. Therefore, targeted reductions in bFGF during therapeutic interventions could enhance treatment outcomes for addiction.
authors.affiliation: Department of Psychology, University of Wisconsin-Milwaukee, Milwaukee, WI, USA.
authors.forename: Madalyn
authors.initials: M
authors.lastname: Hafenbreidel
authors.affiliation: Department of Psychology, University of Wisconsin-Milwaukee, Milwaukee, WI, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Twining
authors.affiliation: Department of Psychology, University of Wisconsin-Milwaukee, Milwaukee, WI, USA.
authors.forename: Carolynn
authors.initials: C
authors.lastname: Rafa Todd
authors.affiliation: Department of Psychology, University of Wisconsin-Milwaukee, Milwaukee, WI, USA.
authors.forename: Devin
authors.identifier: http://orcid.org/0000-0002-7397-9219
authors.initials: D
authors.lastname: Mueller
mesh_terms: D000818:Animals; D002491:Central Nervous System Agents / Q000494:pharmacology*; D003042:Cocaine / Q000008:administration & dosage; D019970:Cocaine-Related Disorders / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage; D058999:Drug-Seeking Behavior / Q000187:drug effects* / Q000502:physiology; D005108:Extinction, Psychological / Q000187:drug effects* / Q000502:physiology; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D020318:Rats, Long-Evans; D012646:Self Administration
chemical_list: D002491:Central Nervous System Agents; D018765:Dopamine Uptake Inhibitors; D016222:Fibroblast Growth Factor 2; D003042:Cocaine