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Pastor R, Sanchis-Segura C, Aragon CM: Ethanol-stimulated behaviour in mice is modulated by brain catalase activity and H2O2 rate of production. Psychopharmacology. 2002 Dec;165(1):51-9. Epub 2002 Oct 25.
RATIONALE: Over the last few years, a role for the brain catalase-H (2) O (2) enzymatic system has been suggested in the behavioural effects observed in rodents after ethanol administration. This role seems to be related to the ability of cerebral catalase to metabolise ethanol to acetaldehyde using H (2) O (2) as a co-substrate. On the other hand, it has been shown that normobaric hyperoxia increases the rate of cerebral H (2) O (2) production in rodents in vivo. Thus, substrate-level changes could regulate brain catalase activity, thereby modulating the behavioural effects of ethanol. OBJECTIVES: The aim of the present study was to assess if the enhancement of cerebral H (2) O (2) production after hyperoxia exposure results in a boost of ethanol-induced locomotion in mice. METHODS: CD-1 mice were exposed to air or 99.5% O (2) inhalation (for 15, 30, or 45 min) and 0, 30, 60 or 120 min after this treatment, ethanol-induced locomotion was measured. The H (2) O (2)-mediated inactivation of endogenous brain catalase activity following an injection of 3-amino-1,2,4-triazole was used as a measure of the rate of cerebral H (2) O (2) production. RESULTS: Hyperoxia exposure (30 or 45 min) potentiated the locomotor-stimulating effects of ethanol (2.5 or 3.0 g/kg), whereas cocaine (4 mg/kg) or caffeine (15 mg/kg)-induced locomotion and blood ethanol levels were unaffected. Moreover, the results also confirmed brain H (2) O (2) overproduction in mice. CONCLUSIONS: The present results suggest that an increase in brain H (2) O (2) production potentiates ethanol-induced locomotion. Therefore, this study provides further support for the notion that the brain catalase-H (2) O (2) system, and by implication centrally formed acetaldehyde, plays a key role in the mediation of ethanol's psychopharmacological effects. |
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