1. Effects of nitric oxide synthase inhibition in the dorsolateral periaqueductal gray matter on ethanol withdrawal-induced anxiety-like behavior in rats.
- Author
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Bonassoli VT, Contardi EB, Milani H, and de Oliveira RM
- Subjects
- Animals, Anxiety enzymology, Anxiety physiopathology, Anxiety psychology, Male, Nitric Oxide metabolism, Periaqueductal Gray enzymology, Periaqueductal Gray physiopathology, Rats, Rats, Wistar, Substance Withdrawal Syndrome enzymology, Substance Withdrawal Syndrome physiopathology, Substance Withdrawal Syndrome psychology, Anxiety etiology, Behavior, Animal drug effects, Ethanol adverse effects, Nitric Oxide Synthase Type II antagonists & inhibitors, Periaqueductal Gray drug effects, Substance Withdrawal Syndrome complications
- Abstract
Rationale: 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., Objectives: 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.
- Published
- 2013
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