Protective effect of pregnanolone against lipoperoxidation and free radicals generation induced in hypothalamus of ovariectomized rats submitted to CO2 exposure.

Several studies support an association between gonadal hormones and oxidative state. This study aimed to determine the consequence of the absence of ovarian hormones on the oxidative status of animals submitted to acute stress induced by CO(2) inhalation. We also evaluated the effect of pregnanolone administration upon the oxidative status in distinct brain structures of ovariectomized (OVX) rats exposed to CO(2). Female rats were divided into intact and OVX and exposed or unexposed to CO(2). Oxidative status was evaluated by 2',7'-dichlorofluorescein (DCF) assay, assessment of malondialdehyde (MDA), as an indicator of lipoperoxidation (through the thiobarbituric acid-reactive substances assay, TBARS), and the total antioxidant reactivity (TAR). Both DCF and TBARS were increased in the hypothalamus of animals submitted to OVX and stress. Nevertheless, free radical production and MDA levels were not affected in either condition alone. In the cerebral cortex, lower MDA levels were observed in OVX animals. Pregnanolone administered to rats submitted to CO(2)+OVX resulted in reduced MDA levels and free radicals production in hypothalamus. We suggest that ovarian hormones may protect the hypothalamus against oxidative stress, particularly when the animals are submitted to challenges. Pregnanolone may protect, at least in part, the hypothalamus of OVX rats from oxidative stress.

Reduction of hippocampal Na+, K+-ATPase activity in rats subjected to an experimental model of depression.

The effect of a model of depression using female rats on Na+, K+-ATPase activity in hippocampal synaptic plasma membranes was studied. In addition, the effect of further chronic treatment with fluoxetine on this enzyme activity was verified. Sweet food consumption was measured to evaluate the efficacy of this model in inducing a state of reduced response to rewarding stimili. After 40 days of mild stress, a reduction in sweet food ingestion was observed. Reduction of hippocampal Na+, K+-ATPase activity was also observed. Treatment with fluoxetine increased this enzyme activity and reversed the effect of stress. Chronic fluoxetine decreased the ingestion of sweet food in both groups. This result is in agreement with suggestions that reduction of Na+, K+-ATPase activity is a caracteristic of depressive disorders. Fluoxetine reversed this effect. Therefore it is possible that altered Na+, K+-ATPase activity may be involved in the pathophysiology of depression in patients.