Objective:

Here, we study the role of NE on spatial learning and memory in rats using a Barnes maze assay.

Background:

The role of norepinephrine (NE) in learning and memory has been extensively studied, yet its contribution to different phases of memory, such as consolidation or updating, remains elusive. 

Design/Methods:

We used a specific noradrenergic neurotoxin (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4)) to deplete central NE stores. In experiment one, Wistar rats (n=16/sex) were trained to reach a hidden goal box using visual and auditory cues for five days with three trials per day. Rats were administered 50 mg/kg/i.p of DSP-4 or saline ten days prior to training on the Barnes maze assay. DSP-4 mediated reduction of NE, but not serotonin or dopamine, was confirmed using HPLC in several brain regions. In experiment two, using female and male rats (n=16/sex), we replicated results of experiment one by utilizing two trials per day to increase the difficulty of learning the task and extended the findings by utilizing a single probe trial (memory consolidation) and a two-day reversal (memory updating) learning task. 

Results:

In experiment one, female and male rats in DSP-4 and saline groups learned the location of the hidden zone, and this was measured by a reduction in latency to reach the goal box. Levels of NE were significantly lower in the dorsal hippocampus, cingulate cortex, and the striatum. Experiment two replicated these results and the subsequent behavioral analysis suggests that only male DSP-4 treated rats increased time spent in the covered hidden zone area during the probe trial.  During the reversal learning task, DSP-4 treated males continued to visit the previously hidden platform despite learning the new goal location. 

Conclusions: