The present study was performed to validate a spatial working memory task using pharmacological manipulations. The water escape T-maze combines the advantages of the Morris water maze and the T-maze while minimizing the disadvantages. Scopolamine (1mg/kg), a drug that affects cognitive function in spatial working memory tasks, significantly decreased the rats' performance in the present delayed alternation task. Glutamate neurotransmission plays an important role in the maintenance of working memory; rats treated with dizocilpine (MK-801; 0.125-0.25mg/kg), a N-methyl-d-aspartate (NMDA) receptor antagonist, were impaired in this task. In agreement with evidence showing a functional interaction between ionotropic and metabotropic glutamatergic receptors, 2-methyl-6-(phenylethynyl)-pyridine (MPEP), a mGlu(5) receptor antagonist, at a dose (1mg/kg) which by itself had no significant effects, enhanced MK-801-induced impairments of spatial working memory. These evidences suggest that the water escape T-maze might be a valid method to assess spatial working memory, sensitive to pharmacological manipulations
