Beneficial effect of the sigma(1) receptor agonist PRE-084 against the spatial learning deficits in aged rats

Sigma(1) (sigma(1)) receptor agonists showed anti-amnesic properties in pharmacological amnesia models. We now investigated whether the selective sigma(1) receptor agonist, 2-(4-morpholinoethyl)-1-phenylcyclohexane-1-carboxylate hydrochloride (PRE-084), could ameliorate spatial learning in aged animals, using a water-maze procedure. Wistar rats, 3 or 24 months old, were trained to locate a visible platform and then an invisible platform. Finally, a transfer test was performed during saline or PRE-084 treatment. Aged, but not adult, animals showed learning deficits unrelated to visual impairments. The PRE-084 treatment allowed aged animals to learn the new platform location, in terms of decreased latencies to the platform during training and increased presence in the quadrant during retention. The results of these experiments suggest a potential of selective sigma(1) receptor agonists as cognitive enhancers during ageing.