RATIONALE: Intermittent swim stress (ISS) produces deficits in swim escape learning and increases immobility in the forced swim test (FST). A previous attempt to reverse this immobility with the selective serotonin reuptake inhibitor (SSRI), fluoxetine (FLX), was unsuccessful, but the sensitivity of this immobility to other types of antidepressants is unknown. OBJECTIVES: In experiment 1, we evaluate the ability of the norepinephrine (NE) selective reuptake inhibitor (NSRI), desipramine (DES), to reverse the ISS-induced immobility in the FST compared to confined controls (CC), while in experiment 2, we test the efficacy of either the SSRI or NSRI to reverse the immobility produced by either ISS or continuous swim (CS)/FST. METHODS: Rats were exposed to their respective behavioral pretreatment (ISS, CS/FST, or CC) and were then injected with an antidepressant or saline solution 23.5, 5, and 1 h prior to the FST. RESULTS: In experiment 1, DES reduced immobility and increased the climbing behavior in the ISS group without altering these behaviors in the CC, while in experiment 2, the CS/FST-induced immobility was reduced by both antidepressants (i.e., FLX and DES), while the ISS-induced immobility was only affected by DES. CONCLUSIONS: These results suggest that the ISS-induced immobility is mediated through the NE system and may represent a model for atypical depression.