Impairment of working memory induced by scopolamine in rats with noradrenergic DSP-4 lesions.

In a working memory task with a three-panel runway set-up, DSP-4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine), a noradrenergic neurotoxin, at 50 mg/kg i.p. given 14 days before testing, had no effect on the number of errors (attempts to pass through two incorrect panels of the three-panel gates at four choice points). Working memory errors were significantly increased by scopolamine, a muscarinic receptor antagonist, at 0.32 mg/kg i.p. given 20 min before testing, whereas errors were not affected by the 0.1 mg/kg dose. In rats with noradrenergic DSP-4 lesions, 0.1 mg/kg scopolamine significantly increased the number of working memory errors. However, DSP-4 at 50 mg/kg and scopolamine at 0.1 mg/kg whether they were administered alone or in combination had no effect on reference memory errors. These results suggest that noradrenergic deficits aggravate the working memory impairment induced by blockade of muscarinic receptors.