Research reportBehavioral sensitization to ethanol results in cross-sensitization to MK-801 but not to NMDA administered intra-accumbens

In mice, repeated ethanol administration may induce behavioral sensitization - a process of progressive potentiation of its stimulant effects, associated with neuroadaptations in the brain reward system. Few studies have directly investigated the subsequent neuroadaptations in the nucleus accumbens (NAc), the central area of the brain reward system, after chronic ethanol administration. The goal of the present study was to analyze the involvement of accumbal glutamate NMDA receptors in the locomotion behavioral response to an NMDA agonist or to an NMDA antagonist in mice previously treated with ethanol. Swiss Albino mice received repeated daily administrations of 2.2 g/kg ethanol or saline for 21 days. According to their locomotor response on the last day of treatment, ethanol-treated mice were classified into sensitized or non-sensitized groups. They were then submitted to a surgical procedure to implement intra-NAc cannulae. After recovery, mice were challenged with intra-NAc administration of saline and, two days later, with NMDA (NMDA agonist) or MK-801 (NMDA antagonist), having their locomotor activity recorded for 1 h. The administration of NMDA induced similar locomotor behavior in all groups. On the other hand, the administration of 3 μg/side MK-801 induced a significant stimulant effect which was more prominent during the first 15 min in the sensitized group than in the non-sensitized or saline groups. Despite no effect of the agonist administration, only in sensitized mice did we observe cross-sensitization between repeated ethanol treatment and the intra-NAc administration of MK-801.

► There is an important individual variability in behavioral sensitization to ethanol. ► Only some ethanol treated mice develop high levels of behavioral sensitization. ► The intra-NAc administration of NMDA induced similar locomotor activity in all mice. ► In sensitized mice, MK-801 induced a significantly more prominent stimulant effect. ► Ethanol and intra-NAc MK-801 cross-sensitization depends on behavioral sensitization.