Neurosteroids can alter neuronal excitability interacting with specific neurotransmitter receptors, thus affecting several functions such as cognition and emotionality. In this study, we investigated, in adult male rats, the effects of the acute administration of pregnenolone-sulfate (PREGS) (10 mg/Kg, s. c.) on cognitive processes using the Can test, a non aversive spatial/visual task which allows the assessment of spatial information-acquisition during the baseline training, and of memory retention in the longitudinal study. Furthermore, on the basis of PREGS pharmacological profile, the modulation of depressive-like behaviour was also evaluated in the forced swim test (FST). Our results indicate that acute PREGS induces: an improvement in spatial orientation-acquisition and in reference memory, during the baseline training; a strengthening effect on reference and working memory during the longitudinal study. A decrease in immobility time in the FST has also been recorded. In conclusion, PREGS exerts enhancing properties on acquisition, consolidation and retrieval of spatial information, probably due of improved hippocampal-dependent memory processes. The additional antidepressant effect observed in the FST can provide further evidence in support of the potential of PREGS as a therapeutic tool for the treatment of cognitive deficits associated with mood disorders.

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