Intermittent swim stress (ISS) exposes a rat to cold water and the effects of the procedure produce detrimental results on activity measures 24h later. The ISS model can be used with the Morris water maze (MWM) to investigate the impact of stress on a spatial learning and memory task, known to involve the hippocampus. We investigated if the ISS model produced performance deficits in the MWM (experiments 1 and 2). We also investigated the role of norepinephrine by using an alpha-2 adrenergic agonist (i.e., clonidine) to exacerbate ISS-induced deficits (experiment 3), and using antidepressants (i.e., desipramine and reboxetine) that enhance the synaptic availability of norepinephrine to reduce ISS-induced deficits (experiments 4 and 5). Results indicated a main effect for stress in all experiments, with the exception of experiment 2, as ISS did induce performance deficits in the MWM. Clonidine enhanced ISS-induced deficits only in the learning trials, while desipramine and reboxetine reduced ISS-induced deficits in the learning trials. Additionally, only reboxetine reduced memory deficits in the MWM. These findings provide evidence that norepinephrine may act as a partial mediator of ISS-induced deficits in MWM performance.