title: Increased operant responding for ethanol in male C57BL/6J mice: specific regulation by the ERK1/2, but not JNK, MAP kinase pathway.
abstract: BACKGROUND
  Extracellular signal-regulated protein kinase (ERK(1/2)) is a member of the mitogen-activated protein kinase (MAPK) signaling pathway and a key molecular target for ethanol (EtOH) and other drugs of abuse.
  
  
  OBJECTIVE
  The aim of the study was to assess the role of two MAPK pathways, ERK(1/2) and c-Jun N-terminal kinase (JNK), on the modulation of EtOH and sucrose self-administration.
  
  
  METHODS
  C57BL/6J mice were trained to lever press on a fixed-ratio 4 schedule with 9% EtOH/2% sucrose, or 2% sucrose, as the reinforcer. In experiments 1 and 2, mice were injected with the MEK(1/2) inhibitor SL 327 (0-100 mg/kg) and the JNK inhibitor AS 6012452 (0-56 mg/kg) prior to self-administration. In experiment 3, SL 327 (0-100 mg/kg) was administered prior to performance on a progressive ratio (PR) schedule of EtOH reinforcement. In experiment 4, SL 327 and AS 601245 were injected 2 h before a locomotor test.
  
  
  RESULTS
  SL 327 (30 mg/kg) significantly increased EtOH self-administration without affecting locomotion. Higher doses of SL 327 and AS 601245 reduced EtOH-reinforced responding and locomotor activity. Reductions of both ligands on sucrose self-administration were due to decreases in motor activity. SL 327 pretreatment had no effect on PR responding.
  
  
  CONCLUSIONS
  ERK(1/2) activity is more directly involved in modulating the reinforcing properties of EtOH than JNK activity due to its selective potentiation of EtOH-reinforced responding. The specificity of this effect to EtOH self-administration, rather than sucrose self-administration, suggests that the mechanism by which ERK(1/2) increases EtOH-reinforced responding does not generalize to all reinforcing solutions and is not due to increased motivation to consume EtOH.
authors.affiliation: Department of Psychiatry, Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Faccidomo
authors.forename: Joyce
authors.initials: J
authors.lastname: Besheer
authors.forename: P Crystal
authors.initials: PC
authors.lastname: Stanford
authors.forename: Clyde W
authors.initials: CW
authors.lastname: Hodge
mesh_terms: D000097:Acetonitriles / Q000494:pharmacology; D000428:Alcohol Drinking / Q000523:psychology*; D000607:Aminoacetonitrile / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D052160:Benzothiazoles / Q000494:pharmacology; D002492:Central Nervous System Depressants / Q000008:administration & dosage*; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D012054:Reinforcement, Psychology; D012646:Self Administration; D013395:Sucrose / Q000008:administration & dosage; D013549:Sweetening Agents / Q000008:administration & dosage
chemical_list: C489138:1,3-benzothiazol-2-yl(2-((2-(3-pyridinyl)ethyl)amino)-4-pyrimidinyl)acetonitrile; D000097:Acetonitriles; D052160:Benzothiazoles; D002492:Central Nervous System Depressants; C424127:SL 327; D013549:Sweetening Agents; D000607:Aminoacetonitrile; D000431:Ethanol; D013395:Sucrose; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases