Consequences of selective blockade of septal noradrenergic afferents on anxiety and spatial working memory performance in mice

This experiment was designed to investigate the role of septal noradrenergic (NA) afferents in the control of anxiety and spatial working memory. To this end, C57B1/6 mice were infused bilaterally into the lateral septal nuclei with 500 ng/0.2 mu l of BE 2254, a selective alpha 1 postsynaptic adrenoceptor antagonist. The consequences of this reversible treatment were evaluated 20 min later on the anxiety level measured in an elevated plus-maze and on spatial working memory, evaluated under four different conditions via the learning of a delayed nonmatching to place (DNMTP) rule achieved in an eight-arm radial maze. In these conditions, the BE 2254, as well as the saline-injected control group, showed an elevation of the anxiety level that may be the indirect expression of a nonspecific septal dysfunction induced by the vehicle injection rather than the normal behavioral response produced by the decrease of septal NA activity. This septal dysfunction also impaired spatial working memory but only when mnesic difficulty of the task is increased, suggesting that this impairment expresses a general memory deficit rather than a working memory deficit per se. A lack of spatial working memory deficits in BE 2254 or saline-injected animals was also observed in two other conditions of the behavioral protocol. However, when treatments were applied before the first exposure of animals to the radial maze (exploration session), only the group which received BE 2254 was impaired during the acquisition session for the rule performed 24 h later. This delayed perturbation seems to be linked, at this stage of the learning procedure, to the lack of NA-dependent processes taking place during the exploration session. Taken together, these data suggest that septal NA mechanisms are more essential at initial stage of this learning, when animals process new features of the situation, than during the expression of spatial working memory per se.