Acute administration of 3-nitropropionic acid, a reactive oxygen species generator, boosts ethanol-induced locomotor stimulation. New support for the role of brain catalase in the behavioural effects of ethanol.
The antioxidant enzyme catalase by reacting with H(2)O(2), forms the compound known as compound I (catalase-H(2)O(2)). This compound is able to oxidise ethanol to acetaldehyde in the CNS. It has been demonstrated that 3-nitropropionic acid (3-NPA) induces the activity of the brain catalase-H(2)O(2) system. In this study, we tested the effect of 3-NPA on both the brain catalase-H(2)O(2) system and on the acute locomotor effect of ethanol. To find the optimal interval for the 3-NPA-ethanol interaction mice were treated with 3-NPA 0, 45, 90 and 135min before an ethanol injection (2.4mg/kg). In a second study, 3-NPA (0, 15, 30 or 45mg/kg) was administered SC to animals 90min before saline or several doses of ethanol (1.6 or 2.4g/kg), and the open-field behaviour was registered. The specificity of the effect of 3-NPA (45mg/kg) was evaluated on caffeine (10mg/kg IP) and cocaine (4mg/kg)-induced locomotion. The prevention of 3-NPA effects on both ethanol-induced locomotion and brain catalase activity by L-carnitine, a potent antioxidant, was also studied. Nitropropionic acid boosted ethanol-induced locomotion and brain catalase activity after 90min. The effect of 3-NPA was prevented by l-carnitine administration. These results indicate that 3-NPA enhanced ethanol-induced locomotion by increasing the activity of the brain catalase system.
Manrique
Héctor M
HM
Area de Psicobiologia, Universitat Jaume I, Castelló, Spain.
Miquel
Marta
M
Aragon
Carlos M G
CM
D000079:Acetaldehyde / Q000378:metabolism*; D000640:Amitrole / Q000494:pharmacology; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D002110:Caffeine / Q000494:pharmacology; D002331:Carnitine / Q000494:pharmacology; D002374:Catalase / Q000037:antagonists & inhibitors / Q000502:physiology*; D004357:Drug Synergism; D004734:Energy Metabolism / Q000187:drug effects; D000431:Ethanol / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000378:metabolism; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D051379:Mice; D008959:Models, Neurological; D009043:Motor Activity / Q000187:drug effects*; D009574:Nitro Compounds / Q000494:pharmacology*; D016877:Oxidants / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects; D011422:Propionates / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology
D009574:Nitro Compounds; D016877:Oxidants; D011422:Propionates; D017382:Reactive Oxygen Species; D016194:Receptors, N-Methyl-D-Aspartate; D002110:Caffeine; D000431:Ethanol; D006861:Hydrogen Peroxide; D002374:Catalase; D000079:Acetaldehyde; C015392:3-nitropropionic acid; D002331:Carnitine; D000640:Amitrole