Long maternal separation accelerates behavioural sensitization to ethanol in female, but not in male mice.

Early life stress is associated with dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis, and with aspects involved in drug abuse. In this study, we investigated the effects of brief (BMS) and long maternal separation (LMS) on the HPA axis response and behavioural sensitization to ethanol (EtOH) in male and female mice. From PND 2 to 14, pups were subjected to daily maternal separation for 15 min (BMS) or 180 min (LMS) or no separated, only handled during cage cleaning (animal facility rearing-AFR). As adults, animals were treated every other day with saline (SAL) or EtOH (2.2g/kg), i.p., for 10 days, and immediately after each administration, their locomotor response was evaluated for 15 min. Forty-eight hours after the 5th administration, all animals were challenged with saline, followed 48 h later, by an EtOH challenge. Corticosterone (CORT) plasma levels were determined 3 times: basal, after the 1st administration and after the EtOH challenge. LMS females showed higher CORT levels than BMS females at basal, but not in response to acute or chronic EtOH administration. The CORT response to EtOH was more robust in LMS and BMS male than AFR male mice. Repeated EtOH treatment induced behavioural sensitization in all groups of male mice. In females, LMS induced a faster sensitization, although BMS females also exhibited behavioural sensitization (4th day and 5th day of treatment, respectively). In conclusion, LMS and BMS produced gender-dependent effects. In females, LMS and BMS facilitated the development of behavioural sensitization, but in the LMS group this effect occurred faster, which may represent increased vulnerability to drug abuse. Moreover, LMS females showed higher basal CORT levels compared to BMS. In males, LMS and BMS increased the CORT response to EtOH but did not modify behavioural sensitization. Therefore, we postulate that LMS female mice exhibited a faster development of behavioural sensitization, but CORT levels were not involved with this effect.

Does scopolamine block the development of ethanol-induced behavioral sensitization?

BACKGROUND: The cholinergic system is important in learning processes and probably influences behavioral sensitization to drugs. This study examined the effects of scopolamine (scop), a muscarinic antagonist, on the behavioral sensitization to ethanol (EtOH) stimulant effect in mice. METHODS: In experiments 1 and 2, male Swiss albino mice received saline or 1.0 mg/kg scop (s.c.) + saline or EtOH (i.p). (1.0 g/kg in experiment 1 and 2.2 g/kg in experiment 2), for 21 days. Locomotor activity (LA) was recorded once a week, being the treatment withdrawn for 7 days after the last test. On the 28th day (challenge 1), they were evaluated under saline or EtOH. In experiment 2, 3 days after the first challenge, they were tested in an open-field arena, under saline or 2.2 g/kg EtOH. Three days after this, mice were tested under saline or 1.0 mg/kg scop in the activity cages. RESULTS: Acutely, EtOH and scop did not alter the LA. However, when both drugs were coadministered, a significant reduction was observed. During the treatment, tolerance to the depressor effect was developed and behavioral sensitization observed only in the saline + 2.2 EtOH group. In challenge 1, the groups scop + 1.0 EtOH, saline + 2.2 EtOH, and scop + 2.2 EtOH presented higher levels of LA than that of the control groups. However, in challenge 2, conducted in a different setting, no differences between groups were observed. In challenge 3, when the animals received scop, both groups pretreated with 2.2 g/kg EtOH (saline + 2.2 EtOH and scop + 2.2 EtOH groups) presented higher levels of activity suggesting an interaction between EtOH and scop. CONCLUSIONS: Although the coadministration of scopolamine had impaired the observation of sensitization on the 21st day test, when the group scop + EtOH was challenged with scop + EtOH, it seems that the scop just masked the observation, but did not impair the development, of the EtOH-sensitization observed in the challenge with EtOH alone. The higher levels of LA in groups pretreated with EtOH only in the cages but not in the open-field arena confirm the importance of environmental factors, such as the context of drug administration and testing.

Oxidative stress induced by intense and exhaustive exercise impairs murine cognitive function.

It has been shown that exercise is helpful against brain disorders. However, this may not be true for intense exercise (IE). Because it is easy to misadjust exercise intensity with physical condition, it is essential to know the effects of IE on cognitive process because it may have important consequences on people skills and work skills. We investigated the effects of IE on male C57Bl/6 mice, 3-mo-old, undergoing 10 days of intense and exhaustive running program on cognition and its possible relationship with brain oxidative stress. Cognition was evaluated by three different cognitive tests: passive avoidance task, contextual fear conditioning, and tone fear conditioning, performed 24 h after the last exercise session. Brain oxidative stress was evaluated by lipid peroxidation and protein oxidation. There was a remarkable memory reduction of exercised animals in comparison with the control group, associated with increase in the brain oxidative stress, with no alterations in shock sensitivity, locomotion and anxiety parameters. Concurrent vitamin C and E supplementation fully prevented the memory decrement induced by IE and partially recovered both the increased the brain lipid peroxidation and the protein oxidation. In conclusion, IE-induces a high index of brain oxidative stress and impairs memory in murine model that was prevented by vitamin C and E supplementation.

Can energy drinks reduce the depressor effect of ethanol? An experimental study in mice.

Although the popularization of the combined use of alcoholic beverages and energy drinks (ED) containing caffeine, taurine and other substances has increased, there are no controlled experimental studies on the effects of ED alone or combined with ethanol. This work aimed at evaluating the effects of different doses of ED combined or not with ethanol, on the locomotor activity of Swiss mice. The administration of 3.57, 10.71 or 17.86 ml/kg of ED alone increased the locomotor activity of the animals in relation to a control group. Low doses of ethanol (0.5, 1.0 and 1.5 g/kg) alone or in combination with 10.71 ml/kg of ED did not affect their locomotor activity. However, the reduction of activity observed after 2.5 g/kg of ethanol was antagonized by 10.71 ml/kg of ED. Further studies on the mechanisms of this interaction are still needed.