Alcohol hangover:impairments in behavior and bioenergetics in central nervous system

Alcohol hangover(AH)is defined as the temporary state after alcohol binge-like drinking,starting when EtOH is absent in plasma.Results from our laboratory have shown behavioral impairments and mitochon-drial dysfunction in an experimental model of AH in mice.Our model consisted in a single i.p.injection of EtOH(3.8 g/kg BW)or saline solution in male and female mice,sacrificing the animals 6 hours after injection.Motor and affective behavior together with mitochondrial function and free radical production were evaluated in brain cortex and cerebellum during AH.Results showed that hangover animals exhibited a significant reduction in neuromus-cular coordination,motor strength and locomotion together with a loss of gait stability and walking deficiencies.Moreover,an increment in anxiety-like behavior together with fear-related phenotype and depression signs were observed.In relation to bioenergetics metabolism,AH induced a reduction in oxygen uptake,inhibition of respira-tory complexes,changes in mitochondrial membrane permeability,decrease in transmembrane potential,increase in O2•-and H2O2 production and impairment in nitric oxide metabolism.All together our data suggest that the phys-iopathological state of AH involves behavioral impairments and mitochondrial dysfunction in mouse brain cortex and cerebellum showing the long lasting effects of acute EtOH exposure in CNS.

Ketamine effect on intracellular and mitochondrial calcium mobilization

The suppressive effects of ketamine on intracellular calcium has been reported in a variety of cells although the mechanisms involved are not well understood.The aim of this work was to evaluate the ketamine effect on the mitochondrial Ca^(2+)accumulation and the cellular Ca^(2+)mobilization using FLUO4-AM and flow cytometry.The results showed that mitochondria from ketamine injected animals presented a lower ability to retain calcium at concentrations higher than 20μM,as compared with controls(saline injected animals).In ad-dition,ketamine showed a significant decreased KCl-induced intracellular calcium concentration.KCl increased calcium influx through cellular depolarization.According to the data presented herein,ketamine presents a clear inhibitory effect on cytosolic Ca2+transport mechanisms,independently from their action on the calcium channel associated NMDA receptor.