Effects of acute amitriptyline administration on memory, anxiety and activity in male and female mice

The effects of acute administration of amitriptyline on memory consolidation in male and female CD1 mice were investigated. Three doses of this tricyclic antidepressant (7.5, 15 and 30 mg/kg) were administered immediately after inhibitory avoidance training. Forty-five minutes after injection, subjects explored the elevated plus-maze for five minutes. Subjects were tested for avoidance twenty-four hours later. Amitriptyline impaired inhibitory avoidance consolidation at doses 7.5, 15 and 30 mg/kg in males, and at doses 7.5 and 30 mg/kg in females. In the elevated plus-maze, amitriptyline had no effect on anxiety (percentage of open arm entries) and induced a dose-dependent impairment of activity (number of closed arm entries). The observed sex differences were limited to subtle stronger effects of amitriptyline in males than in females on inhibitory avoidance. These results indicate that acute amitriptyline administration produces retrograde amnesia on inhibitory avoidance, which does not seem be mediated by anxiolytic effects.