Intermittent ethanol exposure increases long-lasting behavioral and neurochemical effects of MDMA in adolescent mice

Abstract

Juvenile administration of MDMA and alcohol was found to cause a decrease in monoamine levels in adulthood, as well as changes in social interaction behaviors, locomotor activity, increase measures of anxiety in the elevated plus maze (EPM), and decrease step-through latencies in passive avoidance test.

The novelty-seeking phenotype modulates the long-lasting effects of adolescent MDMA exposure

“…On the other hand, when we used a short pattern of MDMA administration during adolescence, we did not observe any changes in anxiety levels 3 weeks after treatment [23]. However, longer MDMA administration during adolescence induced a longlasting anxiogenic effect in mice [24], in accordance with the results obtained by Faria et al [21]. These results suggest that the long-lasting effects of MDMA on anxiety depend on several variables, including the level of novelty-seeking of the animal.…”

“…Although several reports have associated MDMA and aggressive behavior [64], a single administration of MDMA in rats was shown not to affect aggression after 3 weeks [65], although chronic intermittent administration of MDMA during adolescence reduced social behavior and aggression in adult mice [24]. In line with the present results, Wallinga et al [64] reported an increase in aggression 23 days after chronic MDMA treatment only in low aggressive and not in medium or high aggressive rats.…”

“…Control mice were also injected with physiological saline (NaCl 0.9%). Doses were selected based on previous studies [23,24]. For CPP, mice were injected i.p.…”

“…When 6 doses of MDMA were administered on 3 consecutive days, adult mice spent more time engaged in social contacts with their conspecifics [23]. However, when administration was prolonged, adult mice had increased anxiety levels and displayed less social behavior [24]. The rewarding effects of drugs of abuse can also be affected by adolescent exposure to MDMA [16,[25][26][27][28]56].…”

Behavioural and neuroinflammatory effects of the combination of binge ethanol and MDMA in mice

“…A possible explanation might be that acute MDMA (2×20 mg/kg, i.p., at 2-h intervals) per se was not enough to induce significant levels of anxiety whereas it may be able to enhance anxiety-like effects of ethanol absence. On the other hand, experimental studies have found that binge drinking of ethanol is an additional risk factor to develop depressive symptoms (BazarganHejazi et al 2008;Paljärvi et al 2009) and that the brain of adolescent mice exhibited a higher sensitivity to ethanol and MDMA, thus effects of these drugs can be manifested after long-term (White and Swartzwelder 2005;Rodríguez-Arias et al 2011). Moreover, this pattern of drinking during adolescence increases the long-lasting effects of MDMA on the loss of brain DA levels in adulthood .…”