title: Cocaine-related behaviors in mice with deficient gliotransmission.
abstract: BACKGROUND
  Astrocytes play an integral role in modulating synaptic transmission and plasticity, both key mechanisms underlying addiction. However, while astrocytes are capable of releasing chemical transmitters that can modulate neuronal function, the role of these gliotransmitters in mediating behaviors associated with drugs of abuse has been largely unexplored.
  
  
  OBJECTIVE
  The objective of the present study was to utilize mice with astrocytes that lack the ability to release chemical transmitters to evaluate the behavioral consequence of impaired gliotransmission on cocaine-related behaviors. These mice have previously been used to examine the role of gliotransmission in sleep homeostasis; however, no studies to date have utilized them in the study of addictive behaviors.
  
  
  METHODS
  Mice expressing a dominant-negative SNARE protein selectively in astrocytes (dnSNARE mice) were tested in a variety of behavioral paradigms examining cocaine-induced behavioral plasticity. These paradigms include locomotor sensitization, conditioned place preference followed by cocaine-induced reinstatement of CPP, and cocaine self-administration followed by cue-induced reinstatement of cocaine-seeking behavior.
  
  
  RESULTS
  Wild-type and dnSNARE mice demonstrated no significant differences in the development or maintenance of locomotor sensitization. While there were non-significant trends for reduced CPP following a low dose of cocaine, drug-induced reinstatement of CPP is completely blocked in dnSNARE mice. Similarly, while dnSNARE mice demonstrated a non-significant trend toward reduced cocaine self-administration compared with wild-type mice, dnSNARE mice do not demonstrate cue-induced reinstatement in this paradigm.
  
  
  CONCLUSIONS
  Gliotransmission is necessary for reinstatement of drug-seeking behaviors by cocaine or associated cues.
authors.affiliation: Department of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Jill R
authors.initials: JR
authors.lastname: Turner
authors.forename: Laurel E
authors.initials: LE
authors.lastname: Ecke
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Briand
authors.forename: Philip G
authors.initials: PG
authors.lastname: Haydon
authors.forename: Julie A
authors.initials: JA
authors.lastname: Blendy
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects*; D003042:Cocaine / Q000008:administration & dosage* / Q000009:adverse effects; D019970:Cocaine-Related Disorders / Q000378:metabolism / Q000523:psychology; D003216:Conditioning, Operant / Q000187:drug effects; D058999:Drug-Seeking Behavior / Q000187:drug effects*; D005108:Extinction, Psychological / Q000187:drug effects; D005260:Female; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects; D009473:Neuronal Plasticity / Q000187:drug effects; D012055:Reinforcement Schedule; D050600:SNARE Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D012646:Self Administration; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D050600:SNARE Proteins; D003042:Cocaine