Na+,K+-ATPase activity is reduced in hippocampus of rats submitted to an experimental model of depression: Effect of chronic lithium treatment and possible involvement in learning deficits

Lithium and cognitive enhancement: leave it or take it?

“…With respect to stress, chronic lithium pretreatment reportedly reduced stress-induced hypokinesia in the forced swimming test (Kofman et al 1995) and attenuated spatial reference memory deficits in the Morris water maze (Vasconcellos et al 2003). In a later study, lithium also prevented stress-induced reduction in hippocampal Na + /K + -ATPase activity (Vasconcellos et al 2005). These stressrelated neurochemical and cognitive deficits were also reversed by poststress lithium treatment.…”

“…These stressrelated neurochemical and cognitive deficits were also reversed by poststress lithium treatment. Accordingly, it was suggested that Na + /K + -ATPase activity modulation may be one of the mechanisms of lithium's therapeutic action (el-Mallakh 1983;Vasconcellos et al 2005). It must be noted that this study focused on hippocampal Na + /K + -ATPase activity, since this region is particularly sensitive to stress effects.…”

“…Therefore, the possibility that lithium has similar effects on other brain structures cannot be excluded. The variate stress regime used in the two studies mentioned above (Vasconcellos et al 2003(Vasconcellos et al , 2005 was also shown to cause oxidative damage in the hippocampus (Vasconcellos et al 2006b). Although chronic lithium presented some antioxidant properties (decreased free radicals production in hippocampus), it was not able to block the stress-induced oxidative damage (Vasconcellos et al 2006b).…”

“…It also appears to counteract stress-induced lack of response to pleasant stimuli (Vasconcellos et al 2006a). Chronic lithium also appears to protect from, and even reverse, some of the cognitive effects of chronic variate stress, such as the compromise of spatial reference memory in the water maze (Vasconcellos et al 2003(Vasconcellos et al , 2005. In the same paradigm, lithium presented antioxidant properties in the hippocampus (decrease of stress-induced free radicals production), though it was not able to prevent oxidative damage induced by chronic variate stress (Vasconcellos et al 2006b).…”

Chronic Stress and Lithium Treatments Alter Hippocampal Glutamate Uptake and Release in the Rat and Potentiate Necrotic Cellular Death After Oxygen and Glucose Deprivation

“…We have previously observed that chronic stress disrupts the performance of rats in the Morris Water Maze, and that lithium-a widely used drug in the treatment of affective disorders-is able to prevent the impairment induced by chronic stress on spatial memory [9,10]. Considering the well established involvement of glutamatergic neurotransmission in learning and memory processes [11,12], in this study we aimed to evaluate the glutamatergic activity of rats submitted to a chronic variate stress protocol and to a concomitant treatment with lithium, which was measured through evaluation of glutamate release by synaptosomes and glutamate uptake by synaptosomes and slices of hippocampus.…”