L-NAME precipitates catatonia during ethanol withdrawal in rats.
The effect of N(G)-nitro-L-arginine methyl ester (L-NAME), a non-specific inhibitor of nitric oxide (NO) synthase, on catatonia in ethanol dependent rats was investigated. Ethanol was given to rats by a modified liquid diet. An isocaloric liquid diet without ethanol was also given to control rats. L-NAME (50, 100 and 200 mg/kg) and saline were injected intraperitoneally to ethanol-dependent rats 30 min before ethanol withdrawal. Then, catatonia was evaluated by vertical wire test at the 30th min, 2nd, 4th and 6th h of ethanol withdrawal. The injections were repeated 30 min before the observation of 6 h. Locomotor activity was also recorded for 5 min in the same observation intervals. L-NAME (200 mg/kg) or saline were also injected to ethanol non-dependent control rats. L-NAME (50 and 100 mg/kg) inhibited both incidence and intensity of the audiogenic seizures which appeared at 6 h of ethanol withdrawal. L-NAME (200 mg/kg) produced a significant augmentation in both incidence and intensity of the catatonia in ethanol dependent rats. This dose of L-NAME also reduced the locomotor activity of both ethanol dependent and non-dependent rats. The locomotor inhibitory effect was more prominent in ethanol-dependent group. The catatonia precipitating effect of L-NAME was not prevented by L-arginine (1 g/kg, i.p.), a NO precursor, pretreatment. In the naive rats, L-NAME also did not produce catatonia. These results indicate that L-NAME has a catatonia precipitating effect during ethanol withdrawal in rats and this effect seems to be independent from NO mediated mechanisms.
Uzbay
I T
IT
Department of Medical Pharmacology, Psychopharmacology Research Unit, Faculty of Medicine, Gülhane Military Medical Academy, Etlik 06018 Ankara, Turkey. tuzbay@obs.gata.edu.tr
D000161:Acoustic Stimulation; D000428:Alcohol Drinking / Q000523:psychology; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002389:Catatonia / Q000139:chemically induced* / Q000523:psychology; D002492:Central Nervous System Depressants / Q000009:adverse effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D000431:Ethanol / Q000009:adverse effects*; D009043:Motor Activity / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052248:Nitric Oxide Synthase Type I; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000523:psychology; D013375:Substance Withdrawal Syndrome / Q000523:psychology*
D002492:Central Nervous System Depressants; D004791:Enzyme Inhibitors; D000431:Ethanol; D001120:Arginine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D019331:NG-Nitroarginine Methyl Ester