title: The mGlu5 receptor regulates extinction of cocaine-driven behaviours.
abstract: BACKGROUND
  There is extensive evidence implicating the metabotropic glutamate 5 (mGlu5) receptor in aspects of addiction-related behaviours.
  
  
  METHODS
  Here, we used a well-characterized line of mGlu5-deficient mice to further examine the role of this receptor in cocaine-driven behaviours. We confirmed the previously reported deficit in hippocampal long-term potentiation and associated spatial learning impairment.
  
  
  RESULTS
  Despite a spatial learning deficit, mGlu5-deficient mice developed and maintained a conditioned place preference to cocaine, suggesting cocaine reward and Pavlovian conditioning are intact in these animals. Notably, however, mGlu5-deficient mice exhibited a marked deficit in the extinction of a cocaine-conditioned place preference compared to wild type littermates. Moreover, in a fixed ratio operant intravenous self-administration paradigm, both genotypes showed similar responding for cocaine over two different doses, while mGlu5-deficient mice displayed enhanced responding on a progressive ratio schedule. In addition, cue-induced drug-seeking after abstinence was exaggerated in mGlu5-deficient mice.
  
  
  CONCLUSIONS
  Collectively, these findings suggest that while the mGlu5 receptor may be involved in mediating the rewarding effects of cocaine, it appears necessary for the extinction of cocaine-driven behaviours.
authors.affiliation: Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Australia.
authors.forename: Michael K
authors.initials: MK
authors.lastname: Bird
authors.affiliation: The John Curtin School of Medical Research & Eccles Institute of Neuroscience, Australian National University, Canberra, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Lohmann
authors.affiliation: Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Australia.
authors.forename: Billy
authors.initials: B
authors.lastname: West
authors.affiliation: Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Australia; Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Robyn M
authors.initials: RM
authors.lastname: Brown
authors.affiliation: Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Australia.
authors.forename: Jeppe
authors.initials: J
authors.lastname: Kirchhoff
authors.affiliation: The John Curtin School of Medical Research & Eccles Institute of Neuroscience, Australian National University, Canberra, Australia.
authors.forename: Clarke R
authors.initials: CR
authors.lastname: Raymond
authors.affiliation: Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Australia. Electronic address: andrew.lawrence@florey.edu.au.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Lawrence
mesh_terms: D000818:Animals; D016739:Behavior, Addictive / Q000235:genetics* / Q000523:psychology*; D003042:Cocaine / Q000008:administration & dosage*; D005108:Extinction, Psychological / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009924:Organ Culture Techniques; D064529:Receptor, Metabotropic Glutamate 5 / Q000502:physiology*; D012646:Self Administration
chemical_list: C578936:Grm5 protein, mouse; D064529:Receptor, Metabotropic Glutamate 5; D003042:Cocaine
keywords: Cocaine; Extinction; Learning; Mice; Reinforcement; mGlu5 receptor