title: The MEK inhibitor SL327 blocks acquisition but not expression of lithium-induced conditioned place aversion: a behavioral and immunohistochemical study.
abstract: BACKGROUND
  Recent evidence involves extracellular signal-regulated kinase (ERK) in positive motivational properties of drugs as determined by conditioned place preference but, to date, its role in conditioned place aversion (CPA) still awaits to be fully characterized.
  
  
  OBJECTIVE
  The aim of this study was to assess whether activated ERK (pERK) plays a role in the acquisition and/or expression of lithium-induced CPA.
  
  
  METHODS
  C57BL/6J mice were subjected to lithium (150 mg/kg)-induced CPA. The role of pERK was determined by administering the mitogen-activating extracellular kinase inhibitor, SL327, (a) 25 and 50 mg/kg, before each exposure to the lithium-associated compartment (acquisition), and (b) 25, 50, and 100 mg/kg, before post-conditioning test (expression). To assess whether ERK is activated by acute lithium and, in distinct experiments, during CPA expression, mice were sacrificed, 30 min after lithium, and immediately after post-conditioning test, respectively, for pERK immunohistochemistry.
  
  
  RESULTS
  Lithium increased pERK-positive neurons in bed nucleus of stria termialis, in central and basolateral amygdala and elicited significant CPA. SL327 (50 mg/kg) significantly prevented its acquisition. In addition, the post-conditioning test of lithium-conditioned mice determined a significant increase of pERK-positive neurons in the dorsal striatum and SL327 (50 mg/kg), administered before post-conditioning test, while failing at the doses of 25, 50, and 100 mg/kg, to affect lithium-induced CPA expression, completely prevented it.
  
  
  CONCLUSIONS
  These results indicate that pERK is critical for acquisition, but not expression, of lithium-induced CPA and that its activation in the dorsal striatum, during expression, is not critical for retrieval of the aversive memory.
authors.affiliation: Department of Toxicology, University of Cagliari, Via Ospedale, 72, 09124, Cagliari, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Longoni
authors.forename: Liliana
authors.initials: L
authors.lastname: Spina
authors.forename: Stefania
authors.initials: S
authors.lastname: Vinci
authors.forename: Elio
authors.initials: E
authors.lastname: Acquas
mesh_terms: D000607:Aminoacetonitrile / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003214:Conditioning, Classical / Q000187:drug effects*; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors*; D007150:Immunohistochemistry; D018021:Lithium Chloride / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D047428:Protein Kinase Inhibitors; C424127:SL 327; D000607:Aminoacetonitrile; D048049:Extracellular Signal-Regulated MAP Kinases; D018021:Lithium Chloride