Anxiolytic-like effects of antidepressants after acute administration in afour-plate test in mice

The four-plate test (FPT) is an animal model of anxiety based on stress cau sed by unconditioned fear. An increase of spontaneous punished behavior was used as a measure to determine the anxiolytic effects of various antidepre ssants (ADs). In the present study, ADs with different mechanisms of action , including tricyclics, selective serotonin reuptake inhibitors (SSRIs), a monoamine oxidase inhibitor (MAOI), and atypicals, were studied in the FPT to evaluate their anxiolytic-like effects following acute administration. T he number of punished crossings was dramatically increased by the SSRIs cit alopram, fluvoxamine, and paroxetine, but not fluoxetine. The mixed 5-HT/NE reuptake inhibitors, milnacipran and venlafaxine, also demonstrated strong antipunishment effects. The specific NE reuptake inhibitors, desipramine a nd maprotiline, and the atypical AD trazodone, enhanced freezing behavior, suggesting anxiogenic-like behavior. It was concluded that, in the FPT, a m odel based on spontaneous response, where animals are exposed to an aversiv e environment from which they can only escape by being motionless, this kin d of behavior might be related to anticipatory anxiety. In this situation, ADs acting preferentially on 5-HT transmission possessed clear anxiolytic l ike effects. The balance between the two transmitters, 5-HT and NE, seemed to be a crucial factor. (C) 2000 Elsevier Science Inc.