Pregnenolone sulphate enhances spatial orientation and object discrimination in adult male rats: Evidence from a behavioural and electrophysiological study

Abstract 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 both spatial orientation–acquisition and object discrimination in a simple and in a complex version of the visual task. Electrophysiological recordings were also performed in vivo , after acute PREGS systemic administration in order to investigate on the neuronal activation in the hippocampus and the perirhinal cortex. Our results indicate that, PREGS induces an improvement in spatial orientation–acquisition and in object discrimination in the simple and in the complex visual task; the behavioural responses were also confirmed by electrophysiological recordings showing a potentiation in the neuronal activity of the hippocampus and the perirhinal cortex. In conclusion, this study demonstrates that PREGS systemic administration in rats exerts cognitive enhancing properties which involve both the acquisition and utilization of spatial information, and object discrimination memory, and also correlates the behavioural potentiation observed to an increase in the neuronal firing of discrete cerebral areas critical for spatial learning and object recognition. This provides further evidence in support of the role of PREGS in exerting a protective and enhancing role on human memory.