Pregnenolone sulphate (PREGS) affects spatial learning and memory in two different cognitive tasks in adult rats. Influence of the emotional state.

Abstract

Pregnenolone sulphate (PREGS) is one of the most potent memory-enhancing neurosteroids in rodent learning studies, also involved in the modulation of the emotional state (Valleè et al 2001). Neurosteroids exert an important role as modulators of the neuronal activity by interacting with different receptors or ion channels (Urani et al 1998). Indeed PREGS acts as negative modulator of GABAA- and as positive modulator of NMDA -receptors. Altered levels of PREGS have also been reported during aging and in human neurodegenerative pathologies like Alzheimer’s disease. The aim of this study was to investigate, in adult male rats, the effects of a single injection of PREGS (10 mg/kg s.c.) on: i) object recognition task, using the Can test, a non aversive, rewarded facilitated spatial/tactile/visual learning task; ii) spatial learning and memory task, using respectively, the training and the reversal phases in the Morris water maze; iii) the anxiety-like behaviour, using the elevated plus maze. Our results show that PREGS is able to significantly increase object recognition in the Can test, two- and 24 hours after the treatment (p<0.05), respective to controls. When rats were exposed to the training period of the Morris Water Maze, PREGS induced an increase in the latency and the distance travelled (p<0.05), while, on the contrary, a decrease in these two parameters was recorded during the reversal period (p<0.01). Time and number of entries in the open arms of the EPM were significantly reduced following PREGS administration as an index of augmented anxiety-like behaviour. In conclusions, our results show that PREGS is able to increase object recognition in the Can test, and memory retention in the reversal phase of the water maze probably due to a facilitatory effect on hippocampal function, exerted by the modulation on GABA-A receptor. The decrease in the learning performance during the training period of the Morris water maze observed following PREGS injection, may be due to the increased emotional state, as assessed also by the EPM test, that the exposure to the swimming session may have provoked. However, further studies are needed to better elucidate PREGS activity as potential memory enhancer compound