title: Brucine suppresses ethanol intake and preference in alcohol-preferring Fawn-Hooded rats.
abstract: OBJECTIVE
  Brucine (BRU) extracted from the seeds of Strychnos nux-vomica L is glycine receptor antagonist. We hypothesize that BRU may modify alcohol consumption by acting at glycine receptors, and evaluated the pharmacodynamic profiles and adverse effects of BRU in rat models of alcohol abuse.
  
  
  METHODS
  Alcohol-preferring Fawn-Hooded (FH/Wjd) rats were administered BRU (10, 20 or 30 mg/kg, sc). The effects of BRU on alcohol consumption were examined in ethanol 2-bottle-choice drinking paradigm, ethanol/sucrose operant self-administration paradigm and 5-d ethanol deprivation test. In addition, open field test was used to assess the general locomotor activity of FH/Wjd rats, and conditioned place preference (CPP) was conducted to assess conditioned reinforcing effect.
  
  
  RESULTS
  In ethanol 2-bottle-choice drinking paradigm, treatment with BRU for 10 consecutive days dose-dependently decreased the ethanol intake associated with a compensatory increase of water intake, but unchanged the daily total fluid intake and body weight. In ethanol/sucrose operant self-administration paradigms, BRU (30 mg/kg) administered before each testing session significantly decreased the number of lever presses for ethanol and the ethanol intake, without affecting the number of sucrose (10%) responses, total sucrose intake, and the number of lever presses for water. Acute treatment with BRU (30 mg/kg) completely suppressed the deprivation-induced elevation of ethanol consumption. Treatment with BRU (10, 20, and 30 mg/kg) did not alter locomotion of FH/Wjd rats, nor did it produce place preference or aversion.
  
  
  CONCLUSIONS
  BRU selectively decreases ethanol consumption with minimal adverse effects. Therefore, BRU may represent a new pharmacotherapy for alcoholism.
authors.forename: Yu-Ling
authors.initials: YL
authors.lastname: Li
authors.forename: Qing
authors.initials: Q
authors.lastname: Liu
authors.forename: Qi
authors.initials: Q
authors.lastname: Gong
authors.forename: Jun-Xu
authors.initials: JX
authors.lastname: Li
authors.forename: Shou-Peng
authors.initials: SP
authors.lastname: Wei
authors.forename: Yan-Ting
authors.initials: YT
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Liang
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Jing
authors.forename: Zheng
authors.initials: Z
authors.lastname: Yong
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Lawrence
authors.forename: Jian-Hui
authors.initials: JH
authors.lastname: Liang
mesh_terms: D000428:Alcohol Drinking / Q000188:drug therapy* / Q000378:metabolism; D000437:Alcoholism / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D000431:Ethanol / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D018009:Receptors, Glycine / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013331:Strychnine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use; D031461:Strychnos nux-vomica / Q000737:chemistry
chemical_list: D018009:Receptors, Glycine; D000431:Ethanol; C083806:brucine; D013331:Strychnine