Strain-dependent modification of behavior following antidepressant treatment.

The effects of repeated antidepressant drug treatment on behavioral outcome in Wistar Kyoto (WKY) rats, a putative animal model of depressive behavior, were compared to Wistar and Sprague-Dawley (SD) rats. Rats were treated with desipramine (norepinephrine [NE] uptake blocker), nomifensine (NE and dopamine [DA] uptake blocker), paroxetine (serotonin [5-HT] uptake blocker) or saline, for 12 days. On Day 11, rats were tested in the Porsolt forced swim test (FST). On Day 12, rats were tested in the open field test (OFT). Stress reactivity was assessed on Day 13 when all rats were exposed to water-restraint ulcerogenic stress. Significant strain differences in behavioral responses to the drug treatments were observed. Control WKY rats showed the typical freezing behavior in the OFT and excessive floating behavior in the FST as compared to Wistar and SD rats. Desipramine and nomifensine decreased immobility and increased swim time in the FST in WKY rats. Nomifensine reduced response latency in the OFT in WKY rats and increased activity in the OFT in WKY and SD rats. None of the drugs altered the FST in SD rats. Following ulcerogenic stress, desipramine was the only antidepressant that decreased ulcer incidence in all rat strains compared to saline controls. These results suggest that the "depressive behavior" in WKY rats may be modified by antidepressants that alter synaptic levels of NE and/or DA, but not 5-HT.