Date of Award

Spring 2006

Project Type


Program or Major


Degree Name

Doctor of Philosophy

First Advisor

Robert C Drugan


Exposure to uncontrollable stress produces a behavioral syndrome that is often described as "behavioral depression" in the rat. Current paradigms for inducing behavioral depression utilize continuous swimming or intermittent electric shock stress. Brown et al., developed a novel strategy that combined these stressors to produce the intermittent swim stress (ISS) protocol. The purpose of this thesis was to define the behavioral outcomes of ISS that resemble behavioral depression and to begin neurochemical characterization of the phenomenon.

Two hallmark features of behavioral depression are immobility, as determined in a Forced Swim Test (FST) and escape learning deficits, as determined by operant tasks such as the shuttlebox test. In Experiment 1, rats were exposed to either ISS or confinement and, 24 hours later, subjected to a swim escape test (SET) designed to analogue the shuttlebox test in a swim context. Prior stress interfered with escape acquisition in the SET.

The results of previous studies suggest that stress causes a temporary activation of the brain serotonin (5-HT) system that is necessary and sufficient for producing behavioral depression. If this hypothesis is true in the ISS paradigm, then enhancing or inhibiting 5-HT transmission during stress should exacerbate or block the development of behavioral depression, respectively. In Experiment 2 the selective 5-HT uptake inhibitor, fluoxetine, was administered prior to ISS or confinement, 24 h later the FST was used to detect behavioral immobility. ISS, but not fluoxetine, significantly increased immobility in the FST. In Experiment 3, the 5-HT uptake enhancer, tianeptine, was administered in place of fluoxetine. Again ISS increased immobility in the FST, but tianeptine had no effect. These results suggested that 5-HT is not a critical mediator of ISS induced behavioral depression. However, some authors have raised concern that tianeptine does not act directly on 5-HT and, therefore, the results of Experiment 3 are difficult to interpret. Experiment 4 utilized the 5-HT synthesis inhibitor, para-chlorophenylaline (PCPA) to deplete 5-HT before stress. PCPA did not alter immobility in the FST. Taken together, these experiments indicate that ISS produces a significant behavioral depression manifested as increased immobility and poor escape learning. Furthermore, the current data do not support the hypothesis that the 5-HT system is a critical substrate of intermittent swim stress. Results are discussed within a framework of the neurobiology of uncontrollable stressors.