title: Cocaine Self-Administration and Extinction Leads to Reduced Glial Fibrillary Acidic Protein Expression and Morphometric Features of Astrocytes in the Nucleus Accumbens Core.
abstract: As a more detailed picture of nervous system function emerges, diversity of astrocyte function becomes more widely appreciated. While it has been shown that cocaine experience impairs astroglial glutamate uptake and release in the nucleus accumbens (NAc), few studies have explored effects of self-administration on the structure and physiology of astrocytes. We investigated the effects of extinction from daily cocaine self-administration on astrocyte characteristics including glial fibrillary acidic protein (GFAP) expression, surface area, volume, and colocalization with a synaptic marker.
  
  
  
  Cocaine or saline self-administration and extinction were paired with GFAP Westerns, immunohistochemistry, and fluorescent imaging of NAc core astrocytes (30 saline-administering and 36 cocaine-administering male Sprague Dawley rats were employed). Imaging was performed using a membrane-tagged lymphocyte protein tyrosine kinase-green fluorescent protein (Lck-GFP) driven by the GFAP promoter, coupled with synapsin I immunohistochemistry.
  
  
  
  GFAP expression was significantly reduced in the NAc core following cocaine self-administration and extinction. Similarly, we observed an overall smaller surface area and volume of astrocytes, as well as reduced colocalization with synapsin I, in cocaine-administering animals. Cocaine-mediated reductions in synaptic contact were reversed by the β-lactam antibiotic ceftriaxone.
  
  
  
  Multiple lines of investigation indicate that NAc core astrocytes exist in a hyporeactive state following cocaine self-administration and extinction. Decreased association with synaptic elements may be particularly meaningful, as cessation of chronic cocaine use is associated with changes in synaptic strength and resistance to the induction of synaptic plasticity. We hypothesize that the reduced synaptic colocalization of astrocytes represents an important maladaptive cellular response to cocaine and the mechanisms underlying relapse vulnerability.
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Scofield
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina.
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina.
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Siemsen
authors.affiliation: Department of Psychology and Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Kati L
authors.initials: KL
authors.lastname: Healey
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina.
authors.forename: Phuong K
authors.initials: PK
authors.lastname: Tran
authors.affiliation: Department of Psychology and Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Woronoff
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina.
authors.forename: Heather A
authors.initials: HA
authors.lastname: Boger
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Kalivas
authors.affiliation: Department of Psychology and Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. Electronic address: reissner@unc.edu.
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Reissner
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D002443:Ceftriaxone / Q000494:pharmacology; D002452:Cell Count; D003042:Cocaine / Q000008:administration & dosage* / Q000494:pharmacology*; D005108:Extinction, Psychological; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis / Q000172:deficiency*; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration; D013569:Synapses / Q000187:drug effects; D016704:Synapsins / Q000378:metabolism
chemical_list: D005904:Glial Fibrillary Acidic Protein; D016704:Synapsins; D002443:Ceftriaxone; D003042:Cocaine
keywords: Astrocyte; Cocaine; Colocalization; GFAP; Nucleus accumbens; Self-administration