Prior exposure to the elevated plus-maze sensitizes mice to the acute behavioral effects of fluoxetine and phenelzine.

A single undrugged experience of the elevated plus-maze modifies future drug responses in the test. The present study investigated the effects of maze-experience on the acute behavioral effects of the monoamine oxidase inhibitor phenelzine and the serotonin reuptake inhibitor fluoxetine. Phenelzine (2.5-12.5 mg/kg) had no clear effect on plus-maze behavior in test-naive Swiss Webster mice, but dose-dependently increased anxiety-like behavior in maze-experienced subjects. Similarly, fluoxetine (5-20 mg/kg) produced non-significant trends for increased anxiety-like behavior in maze-naive mice, but significantly and dose-dependently increased anxiety-like behavior and suppressed locomotor activity in maze-experienced mice. The anxiogenic effects of the benzodiazepine receptor inverse agonist N-methyl-beta-carboline-3-carboxamide (FG 7142) (20 mg/kg) was abolished by prior test experience, suggesting an alteration in gamma-aminobutyric acid (GABA)/benzodiazepine receptor function with maze-experience. However, the benzodiazepine receptor antagonist flumazenil (5-20 mg/kg) produced a silent profile regardless of maze-experience. Present findings provide further evidence demonstrating that prior test history is a critical consideration in mouse studies of anxiety-related behavior.