title: Cocaine-induced glutamate receptor trafficking is abrogated by extinction training in the rat hippocampus.
abstract: BACKGROUND
  It has been demonstrated that long-term exposure to cocaine leads to plastic changes in the brain that contribute to the manifestation of addictive behaviors. While attention has mostly focused on the meso-cortico-limbic pathway, the hippocampus seems to play a role in the craving induced by cues in drug addicts, in particular in cue- and drug-induced reinstatement of cocaine seeking. Since glutamate appears to be critical for context-induced drug seeking behaviors, the major aim of our work was to investigate the expression of hippocampal AMPA and NMDA glutamate receptors following repeated cocaine exposure and during extinction training.
  
  
  METHODS
  We thus employed the yoked control operant paradigm and exposed the animals to contingent or non-contingent cocaine exposure for 2 weeks and sacrificed the animals after the last self-administration (SA) session and following 1 or 10 days of extinction. Protein levels of glutamate receptors were analyzed by Western blotting.
  
  
  RESULTS
  We found increased levels of the main subunits of both NMDA and AMPA receptors in the post-synaptic density (PSD) fraction, but not in the whole homogenate, of the hippocampus of animals repeatedly exposed to cocaine indicating increased trafficking toward the membrane of these receptors. Also, we found that extinction abolished such effect, suggesting that the trafficking was tightly linked to the presence of the psychostimulant.
  
  
  CONCLUSIONS
  These data reveal a novel, previously unappreciated role of glutamate receptors in the action of cocaine and cocaine-extinction behavior in rat hippocampus.
authors.affiliation: Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milano, Italy; Collaborative Center of Department of Antidrug Policies, Presidency of the Council of Ministers, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Caffino
authors.affiliation: Laboratory of Drug Addiction Pharmacology, Department of Pharmacology, Institute of Pharmacology Polish Academy of Sciences, Kraków, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Frankowska
authors.affiliation: Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milano, Italy; Collaborative Center of Department of Antidrug Policies, Presidency of the Council of Ministers, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Giannotti
authors.affiliation: Laboratory of Drug Addiction Pharmacology, Department of Pharmacology, Institute of Pharmacology Polish Academy of Sciences, Kraków, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Miszkiel
authors.affiliation: Laboratory of Drug Addiction Pharmacology, Department of Pharmacology, Institute of Pharmacology Polish Academy of Sciences, Kraków, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Sadakierska-Chudy
authors.affiliation: Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milano, Italy; Collaborative Center of Department of Antidrug Policies, Presidency of the Council of Ministers, Italy; I.R.C.C.S. San Giovanni di Dio-Fatebenefratelli, Brescia, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Racagni
authors.affiliation: Laboratory of Drug Addiction Pharmacology, Department of Pharmacology, Institute of Pharmacology Polish Academy of Sciences, Kraków, Poland; Department of Toxicology, Faculty of Pharmacy, Jagiellonian University, Kraków, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Filip
authors.affiliation: Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milano, Italy; Collaborative Center of Department of Antidrug Policies, Presidency of the Council of Ministers, Italy. Electronic address: Fabio.Fumagalli@unimi.it.
authors.forename: Fabio
authors.initials: F
authors.lastname: Fumagalli
mesh_terms: D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D005108:Extinction, Psychological / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017470:Receptors, Glutamate / Q000502:physiology*; D012646:Self Administration
chemical_list: D017470:Receptors, Glutamate; D003042:Cocaine
keywords: Cocaine; Extinction; Glutamate; Hippocampus; Self-administration