title: Wheel running reduces ethanol seeking by increasing neuronal activation and reducing oligodendroglial/neuroinflammatory factors in the medial prefrontal cortex.
abstract: The therapeutic effects of wheel running (WR) during abstinence on reinstatement of ethanol seeking behaviors in rats that self-administered ethanol only (ethanol drinking, ED) or ED with concurrent chronic intermittent ethanol vapor experience (CIE-ED) were investigated. Neuronal activation as well as oligodendroglial and neuroinflammatory factors were measured in the medial prefrontal cortex (mPFC) tissue to determine cellular correlates associated with enhanced ethanol seeking. CIE-ED rats demonstrated escalated and unregulated intake of ethanol and maintained higher drinking than ED rats during abstinence. CIE-ED rats were more resistant to extinction from ethanol self-administration, however, demonstrated similar ethanol seeking triggered by ethanol contextual cues compared to ED rats. Enhanced seeking was associated with reduced neuronal activation, and increased number of myelinating oligodendrocyte progenitors and PECAM-1 expression in the mPFC, indicating enhanced oligodendroglial and neuroinflammatory response during abstinence. WR during abstinence enhanced self-administration in ED rats, indicating a deprivation effect. WR reduced reinstatement of ethanol seeking in CIE-ED and ED rats, indicating protection against relapse. The reduced ethanol seeking was associated with enhanced neuronal activation, reduced number of myelinating oligodendrocyte progenitors, and reduced PECAM-1 expression. The current findings demonstrate a protective role of WR during abstinence in reducing ethanol seeking triggered by ethanol contextual cues and establish a role for oligodendroglia-neuroinflammatory response in ethanol seeking. Taken together, enhanced oligodendroglia-neuroinflammatory response during abstinence may contribute to brain trauma in chronic alcohol drinking subjects and be a risk factor for enhanced propensity for alcohol relapse.
authors.affiliation: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Sucharita S
authors.initials: SS
authors.lastname: Somkuwar
authors.affiliation: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: McKenzie J
authors.initials: MJ
authors.lastname: Fannon-Pavlich
authors.affiliation: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Atoosa
authors.initials: A
authors.lastname: Ghofranian
authors.affiliation: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Jacqueline A
authors.initials: JA
authors.lastname: Quigley
authors.affiliation: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Rahul R
authors.initials: RR
authors.lastname: Dutta
authors.affiliation: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Melissa H
authors.initials: MH
authors.lastname: Galinato
authors.affiliation: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA. Electronic address: cmandyam@scripps.edu.
authors.forename: Chitra D
authors.initials: CD
authors.lastname: Mandyam
mesh_terms: D000818:Animals; D003463:Cues; D058999:Drug-Seeking Behavior; D004660:Encephalitis / Q000378:metabolism*; D000431:Ethanol / Q000008:administration & dosage*; D005108:Extinction, Psychological / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009836:Oligodendroglia / Q000187:drug effects* / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D017208:Rats, Wistar
chemical_list: D019408:Platelet Endothelial Cell Adhesion Molecule-1; D000431:Ethanol
keywords: Alcohol; BrdU; MBP; MOG; Medial prefrontal cortex; NG2; Olig2; PECAM-1; Reinstatement; Wheel running