title: The immobility produced by intermittent swim stress is not mediated by serotonin.
abstract: Exposure to uncontrollable stressors such as intermittent swim stress (ISS) produces a behavioral syndrome that resembles behavioral depression including immobility in a Forced Swim Test (FST) and escape learning deficits. The results of previous studies suggest that stress causes a temporary sensitization 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. The selective 5-HT uptake inhibitor fluoxetine (FLX) was administered prior to ISS or confinement; 24 h later the FST was used to detect behavioral immobility. ISS, but not FLX, significantly increased immobility in the FST. The purported 5-HT uptake enhancer tianeptine (TPT) was administered in place of FLX. Again ISS increased immobility in the FST, but TPT 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 TPT does not act directly on 5-HT. Therefore, the 5-HT synthesis inhibitor, para-chlorophenylaline (PCPA) was administered to deplete central 5-HT before stress. PCPA did not alter immobility in the FST. Finally, a sub-chronic regimen of FLX given after ISS, but before the FST, was without effect on reversing the ISS-induced immobility. Taken together, these experiments indicate that ISS produces a significant behavioral depression manifested as increased immobility but offer no support of the hypothesis that 5-HT is a critical mediator of these effects.
authors.affiliation: Department of Psychology, Conant Hall, University of New Hampshire, Durham, NH, USA. John.Christianson@colorado.edu
authors.forename: John P
authors.initials: JP
authors.lastname: Christianson
authors.forename: Sarah
authors.initials: S
authors.lastname: Rabbett
authors.forename: Jennifer
authors.initials: J
authors.lastname: Lyckland
authors.forename: Robert C
authors.initials: RC
authors.lastname: Drugan
mesh_terms: D000818:Animals; D001831:Body Temperature; D003345:Corticosterone / Q000097:blood; D003863:Depression / Q000209:etiology*; D010134:Fenclonine / Q000494:pharmacology; D007103:Immobilization; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time; D012701:Serotonin / Q000502:physiology*; D013315:Stress, Psychological / Q000523:psychology*; D013550:Swimming; D013841:Thiazepines / Q000494:pharmacology
chemical_list: D013841:Thiazepines; C050504:tianeptine; D012701:Serotonin; D010134:Fenclonine; D003345:Corticosterone