STIMULATION OF ALPHA-1-ADRENERGIC RECEPTORS FACILITATES SPATIAL-LEARNING IN RATS

The present experiments were designed to examine the effects of alpha- 1 adrenergic stimulation and inhibition on memory encoding and to inve stigate whether the alpha-1 adrenergic and muscarinic cholinergic syst ems interact in the regulation of spatial navigation behavior in the M orris water maze test and we also studied the effects of D-cycloserine , a partial agonist at the glycine binding site on the N-methyl-D-aspa rtate (NMDA) receptor complex, on the performance of scopolamine-treat ed rats in this task. Pre-training subcutaneous administration of St-5 87 (a putative alpha-1 agonist) at 1000 mu g kg(-1) or 1500 mu g kg(-1 ) improved water maze navigation to a hidden platform. Prazosin (an al pha-1 antagonist), 300-2000 mu g kg(-1), did not significantly impair the spatial navigation performance. Pre-training administration of pra zosin 1000 mu g kg(-1), but not 300 mu g kg(-1), slightly potentiated the deficit in water maze navigation seen after scopolamine (200 mu g kg(-1), pre-training intraperitoneal injection). Pre-training administ ration of St-587 at a dose 1500 mu g kg(-1), but not 500 mu g kg(-1), slightly ameliorated the scopolamine-induced (200 mu g kg(-1)) impairm ent in performance of rats. Pre-training administration of prazosin at doses 300 or 1000 mu g kg-l or St-587 at doses 500 mu g kg(-1) or 150 0 mu g kg(-1) did not have any significant influence on the scopolamin e-induced (200 mu g kg(-1)) increase of swimming speed. Furthermore, D -cycloserine at the dose of 300 mu g kg(-1) but not 1000 or 3000 mu g kg(-1) reversed the scopolamine (200 mu g kg(-1)-induced deficit in ac quisition of the water maze task but not the increase in motor output (increased swimming speed). These results indicate that the stimulatio n of alpha-1 adrenoceptors may facilitate the encoding of new informat ion. These findings suggest that alpha-1 adrenergic mechanisms do not participate or at least are not the most critical part of the noradren ergic system in the interaction between noradrenaline and muscarinic r eceptors in the modulation of learning and memory. In addition, these results suggest that D-cycloserine may be effective in alleviating sta tes of central cholinergic hypofunction. (C) 1998 Elsevier Science B.V ./ECNP.