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The behavioral and neuroprotective effects of 17beta-estradiol (E2), on ovariectomized rats treated with a subconvulsive dose (7 mg/kg bw, ip) of kainic acid (KA), were examined. Estradiol was administered either acutely (150 mug/rat, ip) along with KA, 14 days post-ovariectomy, or chronically (sc capsules providing proestrus estrogen levels in serum) starting at ovariectomy. Exploratory behavior, as deduced by sniffing in the open field test, was reduced in KA-treated rats. Both hormonal schemes partially restored sniffing behavior in KA-lesioned subjects. Moreover, acute and chronic E2 administration in KA-treated rats resulted in increased vertical and horizontal activity of these animals in the open field test. Memory for object recognition was reduced following KA and was not restored by hormonal treatments. Acute, but not chronic, E2 coadministration with KA significantly impaired spatial performance in the water maze task, while KA alone had no effect. Both acute and chronic estradiol administration rescued hilar and CA1 neurons from KA-induced cell death. Chronic, but not acute, E2 increased neurofilament immunoreactivity in the mossy fibers of the dentate gyrus neurons, similarly to KA. Our results show that although estradiol administration in KA-treated rats has beneficial effects on cell survival, it has diverse effects on exploratory behavior, object, and spatial memory. Estradiol effects on KA-lesioned animals depended on the duration and timing of exposure to the hormone, implying different mechanisms of hormone actions. Horm Behav

P>The neurochemical profile of the cortex develops in a region and time specific manner, which can be distorted by psychiatric and other neurological pathologies. Pre-clinical studies often involve experimental mouse models. In this study, we determined the neurochemical profile of C57BL/6 mice in a longitudinal study design to provide a reference frame for the normal developing mouse cortex. Using in vivo proton NMR spectroscopy at 14 T, we measured the concentrations of 18 metabolites in the anterior and posterior cortex on postnatal days (P) 10, 20, 30, 60 and 90. Cortical development was marked by alterations of highly concentrated metabolites, such as N-acetylaspartate, glutamate, taurine and creatine. Regional specificity was represented by early variations in the concentration of glutamine, aspartate and choline. In adult animals, regional concentration differences were found for N-acetylaspartate, creatine and myo-inositol. In this study, animals were exposed to recurrent isoflurane anaesthesia. Additional experiments showed that the latter was devoid of major effects on behaviour or cortical neurochemical profile. In conclusion, the high sensitivity and reproducibility of the measurements achieved at 14 T allowed us to identify developmental variations of cortical areas within the mouse cortex.

Stress-related adrenal steroid hormones modulate brain and cognitive function. Electrophysiological studies, including primed burst potentiation and long-term potentiation, have indicated concentration-dependent inverted U-shape effects of corticosterone in hippocampal function and plasticity. Here, we explored the role of corticosterone in the consolidation and long-term retrieval of spatial learning in the Morris water maze task in rats. We postulated that corticosterone actions might be experience-dependent with regard to stimulus intensity, such as differential water temperatures. Indeed, rats trained at 19°C showed a quicker rate of acquisition and better long-term retention than rats trained at 25°C water. In addition, post-training corticosterone levels, on the first training day, were significantly higher in rats in the 19°C group than in the 25°C group. Performance of rats trained at 25°C, but not at 19°C, water was improved by injecting them i.p. with corticosterone immediately after each training session. Thus, the effect of exogenously administered corticosterone appears to be experience-dependent, with the experience-induced corticosterone concentrations as a critical factor determining the cognitive consequences of steroid treatment. Therefore, this work indicates a facilitating corticosterone action, during the post-training period, on the neural mechanisms determining the strength of information storage under acute, physiological conditions.