Forced swim test: What about females?. (December 2015)

• Record Type: Journal Article
• Authors: Kokras, Nikolaos; Antoniou, Katerina; Mikail, Hudu G.; Kafetzopoulos, Vasilios; Papadopoulou-Daifoti, Zeta; Dalla, Christina
• Is Part Of: Neuropharmacology. Volume 99(2015)
• Page Start: 408
• Page End: 421
• Publication Date: 2015-12
• Subjects: Sertraline -- Depression -- Estrous cycle -- Gonadal hormones -- Rat -- Sex differences; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2015.03.016
• Languages: English
• ISSNs: 0028-3908

Abstract

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. Highlights: In naturally cycling females, estrous cycle effect on the forced swim behavior is small. Female and male antidepressant response is similar when females are tested in diestrous. High sertraline dose enhances climbing duration in diestrous II and proestrous. Males and females may be responsive to different doses of the same drug. Uncovering sex differences in the forced swim test requires proper methodology.