title: PPAR Agonists: II. Fenofibrate and Tesaglitazar Alter Behaviors Related to Voluntary Alcohol Consumption.
abstract: BACKGROUND
  In the accompanying article, we showed that activation of peroxisome proliferator-activated receptor alpha (PPARα) signaling by fenofibrate and tesaglitazar decreases ethanol (EtOH) consumption in mice. In this study, we determined the role of these PPAR agonists in EtOH-related behaviors and other actions that may be important in regulating EtOH consumption.
  
  
  METHODS
  The effects of fenofibrate (150 mg/kg) and tesaglitazar (1.5 mg/kg) were examined on the following responses in male and female C57BL/6J (B6) and B6 × 129S4 mice: preference for saccharin, EtOH-induced conditioned place preference (CPP), conditioned taste aversion (CTA), loss of righting reflex, and withdrawal, acoustic startle reflex, response to novelty, and EtOH clearance. Because the B6 inbred strain usually displays weak EtOH-induced CPP and weak EtOH-induced acute withdrawal, B6 × 129S4 mice were also studied.
  
  
  RESULTS
  Fenofibrate and tesaglitazar decreased the novelty response and increased acute EtOH withdrawal severity, and fenofibrate increased EtOH-induced CTA. Two important factors for EtOH consumption (saccharin preference and EtOH-induced CPP) were not altered by fenofibrate or tesaglitazar. EtOH clearance was increased by both fenofibrate and tesaglitazar. Response to novelty, acute withdrawal, and EtOH clearance show sex differences and could contribute to the reduced EtOH consumption following fenofibrate administration.
  
  
  CONCLUSIONS
  These studies indicate the complexity of EtOH-dependent and EtOH-independent behaviors that are altered by PPAR agonists and provide evidence for novel behavioral actions of these drugs that may contribute to PPAR-mediated effects on alcohol drinking.
authors: Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, Texas.
authors: Yuri A
authors: YA
authors: Blednov
authors: Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, Texas.
authors: Mendy
authors: M
authors: Black
authors: Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, Texas.
authors: Jillian M
authors: JM
authors: Benavidez
authors: Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, Texas.
authors: Eleni E
authors: EE
authors: Stamatakis
authors: Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, Texas.
authors: R Adron
authors: RA
authors: Harris
mesh_terms: D000428:Alcohol Drinking / Q000188:drug therapy* / Q000523:psychology; D000476:Alkanesulfonates / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology; D005260:Female; D011345:Fenofibrate / Q000494:pharmacology* / Q000627:therapeutic use; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D047493:PPAR alpha / Q000819:agonists* / Q000502:physiology*; D010666:Phenylpropionates / Q000494:pharmacology* / Q000627:therapeutic use; D057897:Reflex, Righting / Q000187:drug effects / Q000502:physiology; D013649:Taste / Q000187:drug effects / Q000502:physiology
chemical_list: D000476:Alkanesulfonates; D047493:PPAR alpha; D010666:Phenylpropionates; C501413:tesaglitazar; D011345:Fenofibrate
keywords: Conditioned Place Preference; Conditioned Taste Aversion; Ethanol Withdrawal and Sedation; Fenofibrate; Tesaglitazar