Effect of amitriptyline on avoidance learning in rats following olfactory bulb ablation

It has been established that following bilateral olfactory bulb ablation there occurs a performance deficit in rats exposed to aversive learning procedures. Associated with the behavioral deficit, there occurs a reduction in total cortical norepinephrine (NE). If the behavioural deficit observed is a sequitur or correlate of the NE reduction, then drug therapy aimed at increasing NE availability in the cortex should overcome the reduction in performance. Amitriptyline increases NE availability by inhibiting uptake mechanisms and increases the rate of synthesis of NE. Rats, previously bulb ablated, were treated with amitriptyline over a 10 to 14 day period and tested in aversive situations. It was demonstrated that the drug treated rats showed improved performance early in acquisition, and that the performance improvement was maintained when the treatment period was extended to 14 days. These results indicate that amitriptyline was inducing a true pharmacological effect, and that the improved performance could be correlated with increased NE availability in the cerebral cortex.