title: Mice lacking adenylyl cyclase type 5 (AC5) show increased ethanol consumption and reduced ethanol sensitivity.
abstract: BACKGROUND
  The adenylyl cyclase (AC)/cAMP system is believed to be a key component in regulating alcohol-drinking behavior. It was reported that adenylyl cyclase-5 (AC5) is expressed widely in the brain, with a preferential concentration in the dorsal striatum and nucleus accumbens, brain regions which are important for addiction and emotion. AC5 has been shown to be an essential mediator of morphine addiction and dopamine receptor function; however, it remains unknown whether or not AC5 plays a role in ethanol preference and sensitivity in animals.
  
  
  OBJECTIVE
  This work was carried out to determine the role of AC5 in alcohol consumption and the hypnotic response to alcohol using AC5 knockout (KO) mice.
  
  
  RESULTS
  In the test for ethanol preference employing a two-bottle free-choice paradigm, AC5 KO mice showed increased ethanol consumption and preference compared with the wild-type mice. Ethanol-induced hypothermia was weakly reduced in AC5 KO mice. AC5 KO mice exhibited sedation/behavioral sleep to high-dose ethanol, but their responses were greatly suppressed compared with the wild-type mice.
  
  
  CONCLUSIONS
  These results suggest that AC5 is an important signaling molecule regulating alcohol sensitivity and preference in animals. These data provide critical information for AC5 activation as a candidate target for the treatment of alcoholism.
authors.affiliation: Brain Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
authors.forename: Kyoung-Shim
authors.initials: KS
authors.lastname: Kim
authors.forename: Hannah
authors.initials: H
authors.lastname: Kim
authors.forename: In-Sun
authors.initials: IS
authors.lastname: Baek
authors.forename: Ko-Woon
authors.initials: KW
authors.lastname: Lee
authors.forename: Pyung-Lim
authors.initials: PL
authors.lastname: Han
mesh_terms: D000262:Adenylyl Cyclases / Q000172:deficiency* / Q000235:genetics; D000428:Alcohol Drinking / Q000235:genetics / Q000378:metabolism*; D000437:Alcoholism / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D000704:Analysis of Variance; D000818:Animals; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D002755:Choice Behavior / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects; D000431:Ethanol / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D005106:Exploratory Behavior / Q000187:drug effects; D007036:Hypothermia, Induced / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012018:Reflex / Q000187:drug effects
chemical_list: D002492:Central Nervous System Depressants; D000431:Ethanol; D000262:Adenylyl Cyclases; C419510:adenylyl cyclase type V