title: Effects of nitric oxide synthase inhibition in the dorsolateral periaqueductal gray matter on ethanol withdrawal-induced anxiety-like behavior in rats.
abstract: BACKGROUND
  Nitric oxide (NO)-mediated transmission in the dorsolateral periaqueductal gray matter (dlPAG) has been involved in the expression of anxiety-like behaviors. Ethanol withdrawal sensitizes the dlPAG and results in increased anxiety-like responses.
  
  
  OBJECTIVE
  The objective of the study was to test the hypothesis that NO in the dlPAG is involved in the expression of ethanol withdrawal-induced anxiety.
  
  
  METHODS
  Male Wistar rats were implanted with guide cannulae aimed at the dlPAG. The animals were forced to consume a liquid diet containing ethanol 6-8 % (v/v) for 15 days as their only source of diet. Six days after surgery and 24 h after ethanol discontinuation, the animals received microinjections of the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO), nonselective nitric oxide synthase inhibitor N (G)-nitro-L-arginine methyl ester (L-NAME), selective neuronal nitric oxide synthase inhibitor 1-(2-[trifluoromethyl]phenyl) imidazole (TRIM), or selective inducible nitric oxide synthase (iNOS) inhibitor N-([3-(aminomethyl)phenyl]methyl) ethanimidamide dihydrochloride (1400W) into the dlPAG. Ten minutes later, the animals were tested in the light/dark box.
  
  
  RESULTS
  Carboxy-PTIO (1 nmol), L-NAME (200 nmol), TRIM (20 nmol), and 1400W (0.3 and 1 nmol) decreased the anxiogenic-like effects of ethanol withdrawal in rats in the light/dark box test. The NO precursor L-arginine reversed the effects of L-NAME.
  
  
  CONCLUSIONS
  NO production in the dlPAG may play a role in the modulation of ethanol withdrawal-induced anxiety-like behavior in rats. Furthermore, iNOS-mediated NO synthesis in the dlPAG is predominantly involved in the behavioral expression of anxiety-like behavior during ethanol withdrawal.
authors.affiliation: Department of Pharmacology and Therapeutics, State University of Maringá, Av. Colombo, 5790, CEP 87020-900 Maringá, Paraná, Brazil.
authors.forename: Vivian Taciany
authors.initials: VT
authors.lastname: Bonassoli
authors.forename: Ewandro Braz
authors.initials: EB
authors.lastname: Contardi
authors.forename: Humberto
authors.initials: H
authors.lastname: Milani
authors.forename: Rúbia Maria Weffort
authors.initials: RM
authors.lastname: de Oliveira
mesh_terms: D000818:Animals; D001007:Anxiety / Q000201:enzymology / Q000209:etiology* / Q000503:physiopathology / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects*; D000431:Ethanol / Q000009:adverse effects*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors*; D010487:Periaqueductal Gray / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D013375:Substance Withdrawal Syndrome / Q000150:complications* / Q000201:enzymology / Q000503:physiopathology / Q000523:psychology
chemical_list: D009569:Nitric Oxide; D000431:Ethanol; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat