title: Forced swim test: What about females?
abstract: In preclinical studies screening for novel antidepressants, male and female animals should be used. However, in a widely used antidepressant test, the forced swim test (FST), sex differences between males and females are not consistent. These discrepancies may discourage the inclusion of females in FST studies. In order to overcome this problem and provide a detailed insight regarding the use of female animals in the FST, we designed the following experiment and we performed a thorough analysis of the relevant literature. Male and female Wistar adult rats were subjected to the FST and sertraline was used as an antidepressant in two doses (10 mg/kg and 40 mg/kg, 3 injections in 24 h). Rodents were subjected in the two FST sessions during all possible combinations of the estrous cycle stages. We found that females exhibited higher levels of immobility than males and this sex difference was alleviated following antidepressant treatment. Sertraline at both doses enhanced swimming in both sexes, but females appeared more responsive to lower sertraline doses regarding immobility levels. Surprisingly, the high sertraline dose enhanced climbing particularly in proestrous and diestrous. Marked sex differences were also observed in the frequency of head swinging, with females exhibiting lower counts than males. Conclusively, when screening for new antidepressants, it is recommended to use standard FST procedures and if possible to include females in all phases of the cycle. Using only one dose of an investigational drug in females in certain phases of the cycle could result to false negative results.
authors.affiliation: Department of Pharmacology, Medical School, University of Athens, Greece; First Department of Psychiatry, Eginition Hospital, Medical School, University of Athens, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Kokras
authors.affiliation: Department of Pharmacology, Medical School, University of Ioannina, Greece.
authors.forename: Katerina
authors.initials: K
authors.lastname: Antoniou
authors.affiliation: Department of Pharmacology, Medical School, University of Athens, Greece.
authors.forename: Hudu G
authors.initials: HG
authors.lastname: Mikail
authors.affiliation: Department of Pharmacology, Medical School, University of Athens, Greece.
authors.forename: Vasilios
authors.initials: V
authors.lastname: Kafetzopoulos
authors.affiliation: Department of Pharmacology, Medical School, University of Athens, Greece.
authors.forename: Zeta
authors.initials: Z
authors.lastname: Papadopoulou-Daifoti
authors.affiliation: Department of Pharmacology, Medical School, University of Athens, Greece. Electronic address: cdalla@med.uoa.gr.
authors.forename: Christina
authors.initials: C
authors.lastname: Dalla
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D003866:Depressive Disorder / Q000188:drug therapy / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004967:Estrogens / Q000378:metabolism; D030762:Estrous Cycle / Q000187:drug effects* / Q000502:physiology*; D005260:Female; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D011374:Progesterone / Q000378:metabolism; D017208:Rats, Wistar; D020280:Sertraline / Q000494:pharmacology*; D012727:Sex Characteristics; D013550:Swimming / Q000502:physiology* / Q000523:psychology; D013739:Testosterone / Q000378:metabolism
chemical_list: D000928:Antidepressive Agents; D004967:Estrogens; D013739:Testosterone; D011374:Progesterone; D020280:Sertraline
keywords: Depression; Estrous cycle; Gonadal hormones; Rat; Sertraline; Sex differences