title: Effects of acute or repeated paroxetine and fluoxetine treatment on affective behavior in male and female adolescent rats.
abstract: BACKGROUND
  The SSRI antidepressant fluoxetine is one of the few drugs that is effective at treating depression in adolescent humans. In contrast, the SSRI paroxetine has limited efficacy and is more at risk for inducing suicidal behavior.
  
  
  OBJECTIVE
  The purpose of the present study was to more fully characterize the differential actions of paroxetine and fluoxetine.
  
  
  METHODS
  In experiment 1, male and female rats were injected with paroxetine (2.5 or 10 mg/kg), fluoxetine (10 mg/kg), or vehicle for 10 days starting on postnatal day (PD) 35, and affective behaviors were assessed using sucrose preference and elevated plus maze tasks. A separate set of rats were used to examine monoamine levels. In experiment 2, rats were injected with paroxetine (2.5, 5, or 10 mg/kg), fluoxetine (5, 10, or 20 mg/kg), or vehicle during the same time frame as experiment 1, and anxiety-like behaviors were measured using elevated plus maze, light/dark box, and acoustic startle.
  
  
  RESULTS
  Repeated SSRI treatment failed to alter sucrose preference, although both paroxetine and fluoxetine reduced time spent in the open arms of the elevated plus maze and light compartment of the light/dark box. Paroxetine, but not fluoxetine, enhanced acoustic startle and interfered with habituation. Serotonin turnover was decreased by both acute and repeated fluoxetine treatment but unaltered by paroxetine administration.
  
  
  CONCLUSIONS
  These results show that repeated treatment with paroxetine and fluoxetine has dissociable actions in adolescent rats. In particular, paroxetine, but not fluoxetine, increases acoustic startle at low doses and may increase sensitivity to environmental stressors.
authors.affiliation: Department of Psychology, California State University, San Bernardino, CA, 92407, USA.
authors.forename: Leslie R
authors.initials: LR
authors.lastname: Amodeo
authors.forename: Venuz Y
authors.initials: VY
authors.lastname: Greenfield
authors.forename: Danielle E
authors.initials: DE
authors.lastname: Humphrey
authors.forename: Veronica
authors.initials: V
authors.lastname: Varela
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Pipkin
authors.forename: Shannon E
authors.initials: SE
authors.lastname: Eaton
authors.forename: Jelesa D
authors.initials: JD
authors.lastname: Johnson
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Plant
authors.forename: Zachary R
authors.initials: ZR
authors.lastname: Harmony
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Crawford
mesh_terms: D000367:Age Factors; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage*; D001007:Anxiety / Q000188:drug therapy / Q000523:psychology; D003866:Depressive Disorder / Q000188:drug therapy* / Q000523:psychology*; D004334:Drug Administration Schedule; D005260:Female; D005473:Fluoxetine / Q000008:administration & dosage*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D019964:Mood Disorders / Q000188:drug therapy / Q000523:psychology; D017374:Paroxetine / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D055139:Sensory Gating / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D018687:Antidepressive Agents, Second-Generation; D005473:Fluoxetine; D017374:Paroxetine