title: Sex differences in response to oral amitriptyline in three animal models of depression in C57BL/6J mice.
abstract: BACKGROUND
  Knockout and transgenic mice provide a tool for assessing the mechanisms of action of antidepressants. The effectiveness of oral administration of the tricyclic antidepressant amitriptyline (AMI) was assessed in C57BL/6J (B6) mice, a common genetic background on which knockout and transgenic mice are maintained.
  
  
  OBJECTIVE
  We determined whether oral AMI would have antidepressant-like effects in B6 mice and whether these effects varied according to sex, duration of treatment, and the depression model utilized.
  
  
  METHODS
  Male and female B6 mice were administered AMI (200 microg/ml) in the drinking water as the sole source of fluid, along with 2% saccharin to increase palatability. Control mice were administered 2% saccharin alone. Mice were assessed for responsiveness to AMI in the tail suspension test (TST), the forced swim test (FST), and the learned helplessness (LH) paradigm.
  
  
  RESULTS
  In the TST, AMI decreased immobility time regardless of sex or duration of treatment. AMI also decreased immobility time in the FST, but chronic treatment was necessary for full efficacy in both sexes. In the LH paradigm, both subchronic and chronic AMI treatment decreased escape latencies in female mice, but AMI was effective only after chronic treatment in males. The antidepressant-like effects of AMI could not be explained by differences in locomotor activity because activity levels were not altered by antidepressant treatment.
  
  
  CONCLUSIONS
  Overall, oral AMI administration provides a valid model for behavioral assessment of antidepressant-like effects in knockout and transgenic mice maintained on a B6 background, but the effectiveness of oral AMI varies depending on sex, duration of treatment, and the depression model used.
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, 34 Park Street, 3rd Floor Research, New Haven, CT 06508, USA.
authors.forename: B J
authors.initials: BJ
authors.lastname: Caldarone
authors.forename: K
authors.initials: K
authors.lastname: Karthigeyan
authors.forename: A
authors.initials: A
authors.lastname: Harrist
authors.forename: J G
authors.initials: JG
authors.lastname: Hunsberger
authors.forename: E
authors.initials: E
authors.lastname: Wittmack
authors.forename: S L
authors.initials: SL
authors.lastname: King
authors.forename: P
authors.initials: P
authors.lastname: Jatlow
authors.forename: M R
authors.initials: MR
authors.lastname: Picciotto
mesh_terms: D000284:Administration, Oral; D000639:Amitriptyline / Q000494:pharmacology*; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D003866:Depressive Disorder / Q000188:drug therapy* / Q000523:psychology; D004195:Disease Models, Animal; D005260:Female; D006380:Helplessness, Learned; D019417:Hindlimb Suspension; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity; D012737:Sex Factors; D013550:Swimming
chemical_list: D000929:Antidepressive Agents, Tricyclic; D000639:Amitriptyline