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It has been suggested that some of the behavioral effects produced by ethanol are mediated by its first metabolite, acetaldehyde. The present research addressed the hypothesis that catalase-dependent metabolism of ethanol to acetaldehyde in the brain is an important step in the production of ethanol-related affective properties. Firstly, we investigated the contribution of brain catalase in the acquisition of ethanol-induced conditioned place preference (CPP). Secondly, the specificity of the catalase inhibitor 3-amino-1,2,4-triazole (AT) was evaluated with morphine- and cocaine-induced CPP. Finally, to investigate the role of catalase in the process of relapse to ethanol seeking caused by re-exposure to ethanol, after an initial conditioning and extinction, mice were primed with saline and ethanol or AT and ethanol and tested for reinstatement of CPP. Conditioned place preference was blocked in animals treated with AT and ethanol. Morphine and cocaine CPP were unaffected by AT treatment. However, the reinstatement of place preference was not modified by catalase inhibition. Taken together, the results of the present study indicate that the brain catalase-H(2)O(2) system contributes to the acquisition of affective-dependent learning induced by ethanol, and support the involvement of centrally-formed acetaldehyde in the formation of positive affective memories produced by ethanol.

The C57BL/6J strain of inbred mice shows a characteristic pattern of ethanol-induced behaviors: very weak acute locomotor stimulation, a lack of locomotor-sensitizing effect of ethanol, and a high level of ethanol intake. This strain has relatively low levels of activity of the ethanol metabolizing enzyme catalase, and it has been proposed that brain catalase plays a role in the modulation of some behavioral effects of ethanol. In the first study of the present paper, we investigated the effects of pharmacological manipulations of brain catalase activity on C57BL/6J mice in acute ethanol-induced locomotion and ethanol intake. Results indicated that the reduction in motor activity produced by ethanol was reversed by pretreatment with catalase potentiators and it was enhanced by catalase inhibitors. In addition, ethanol intake was highly correlated with brain catalase activity in mice treated with a catalase potentiator. In the second study, F1 hybrid mice (SWXB6) from the outbred Swiss-Webster mice and the inbred C57BL/6J mice were used. Basal brain catalase activity levels of F1 mice were intermediate between to those of the two progenitor genotypes. That profile of catalase activity was parallel to the acute-ethanol-induced locomotion and to repeated-ethanol-induced motor sensitization effects observed across the three types of mice. These data suggest that brain catalase activity modifications in the C57BL/6J strain change the pattern of several ethanol-related behaviors in this inbred mouse.

Anabolic-androgenic steroids are synthetic derivatives of testosterone, which are increasingly abused by adolescent populations who also abuse psychoactive substances. All these compounds lead to complex behavioral syndromes and the effects of their interactions remain unclear. The main aim of the present study was to determine the influence of testosterone on the locomotor activity-promoting effect of cocaine on male mice in an open field. In the three experiments, animals received two injections: firstly, testosterone or peanut oil, and secondly, cocaine or saline solution. In Experiments 1 and 2, testosterone (or oil) and cocaine (or saline) were injected 45 and 10 min, respectively, prior to activity recording. In the first experiment, we studied the effects of testosterone (2 mg/kg) on locomotor activity induced by different doses of cocaine (2, 4, 8, 10 or 12 mg/kg). In Experiment 2, we explored the effects of supraphysiological doses of testosterone (2, 6, 10 or 14 mg/kg) on animals treated with 10 mg/kg cocaine. Finally, in the third experiment, 14 mg/kg testosterone or vehicle was administered 15, 30, 45 or 75 min before activity data collection to animals that received 10 mg/kg cocaine or saline. Testosterone itself had no effects on spontaneous locomotor activity and, as was expected, cocaine increased locomotor activity dose-dependently. Given together, testosterone enhanced the cocaine-induced hyperactivity although not dose-dependently, the highest effects being found 45 min after testosterone injection. The present study confirmed the existence of an interaction between testosterone and cocaine at the central nervous system.

It has been demonstrated that acute administration of lead to mice enhances brain catalase activity and ethanol-induced locomotion. These effects of lead seem to be related, since they show similar time courses and occur at similar doses. In the present study, in an attempt to further evaluate the relation between brain catalase activity and lead-induced changes in ethanol-stimulated locomotion, the interaction between lead acetate and 3-amino-1H,2,4-triazole (AT), a well-known catalase inhibitor, was assessed. In this study, lead acetate or saline was acutely injected intraperitoneally to Swiss mice at doses of 50 or 100 mg/kg 7 days before testing. On the test day, animals received an intraperitoneal injection of AT (0, 10, or 500 mg/kg). Five hours following AT treatment, ethanol (0.0 or 2.5 g/kg, ip) was injected and the animals were placed in open-field chambers, in which locomotion was measured for 10 min. Neither lead exposure nor AT administration, either alone or in combination, had any effect on spontaneous locomotor activity. AT treatment reduced ethanol-induced locomotion as well as brain catalase activity. On the other hand, ambulation and brain catalase activity were significantly increased by both doses of lead. Furthermore, AT significantly reduced the potentiation produced by lead acetate on brain catalase and on ethanol-induced locomotor activity in a dose-dependent manner. A significant correlation was found between locomotion and catalase activity across all test conditions. The results show that brain catalase activity is involved in the effects of lead acetate on ethanol-induced locomotion in mice. Thus, this study confirms the notion that brain catalase provides the molecular basis for understanding some of the mechanisms of the action of ethanol in the central nervous system.