title: Inhibition of phosphodiesterase-4 decreases ethanol intake in mice.
abstract: BACKGROUND
  Cyclic AMP (cAMP)-protein kinase A signaling has been implicated in the regulation of ethanol consumption. Phosphodiesterase-4 (PDE4) specifically hydrolyzes cAMP and plays a critical role in controlling intracellular cAMP levels in the brain. However, the role of PDE4 in ethanol consumption remains unknown.
  
  
  OBJECTIVE
  The objective of this study is to examine whether PDE4 was involved in regulating ethanol intake.
  
  
  METHODS
  The two-bottle choice paradigm was used to assess intake of ethanol, sucrose, and quinine in C57BL/6J mice treated with the selective PDE4 inhibitor rolipram or Ro 20-1724; locomotor activity was also monitored using the open-field test in mice treated with rolipram.
  
  
  RESULTS
  Administration (i.p.) of either rolipram (0.25 and 0.5 mg/kg) or Ro 20-1724 (10 mg/kg) reduced ethanol intake and preference by 60-80%, but did not alter total fluid intake. In contrast, rolipram even at the higher dose of 0.5 mg/kg was not able to affect intake of sucrose or quinine, alcohol-induced sedation, or blood ethanol elimination. At 0.5 mg/kg, rolipram did decrease locomotor activity, but the effect only lasted for approximately 40 min, which did not likely affect behavior of ethanol drinking.
  
  
  CONCLUSIONS
  These results suggest that PDE4 is a novel target for drugs that reduce ethanol intake; PDE4 inhibitors may be used for treatment of alcohol dependence.
authors.affiliation: Department of Behavioral Medicine and Psychiatry, West Virginia University Health Sciences Center, 1 Medical Center Drive, Morgantown, WV 26506-9137, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Hu
authors.forename: Tina
authors.initials: T
authors.lastname: Lu
authors.forename: Alan
authors.initials: A
authors.lastname: Chen
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
authors.forename: Rolf
authors.initials: R
authors.lastname: Hansen
authors.forename: L Judson
authors.initials: LJ
authors.lastname: Chandler
authors.forename: Han-Ting
authors.initials: HT
authors.lastname: Zhang
mesh_terms: D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / Q000008:administration & dosage / Q000494:pharmacology; D000428:Alcohol Drinking / Q000517:prevention & control; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D058988:Phosphodiesterase 4 Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D011803:Quinine / Q000008:administration & dosage; D020889:Rolipram / Q000008:administration & dosage / Q000494:pharmacology*; D013395:Sucrose / Q000008:administration & dosage
chemical_list: D002492:Central Nervous System Depressants; D058988:Phosphodiesterase 4 Inhibitors; D010726:Phosphodiesterase Inhibitors; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone; D000431:Ethanol; D013395:Sucrose; D011803:Quinine; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D020889:Rolipram