Estrous cycle effects on behavior of C57BL/6J and BALB/cByJ female mice: implications for phenotyping strategies

Abstract

Systematic behavioral phenotyping of genetically modified mice is a powerful method with which to identify the molecular factors implicated in control of animal behavior, with potential relevance for research into neuropsychiatric disorders. A number of such disorders display sex differences, yet the use of female mice in phenotyping strategies has been a rare practice because of the potential variability related to the estrous cycle. We have now investigated the behavioral effects of the estrous cycle in a battery of behavioral tests in C57BL/6J and BALB/cByJ inbred strains of mice. Whereas the performance of BALB/cByJ female mice varied significantly depending on the phase of the estrous cycle in the open field, tail flick and tail suspension tests, the behavior of C57BL/6J females, with the exception of the tail suspension performance, remained stable across all four phases of the estrous cycle in all of the tests including open field, rotarod, startle reflex and pre-pulse inhibition, tail flick and hot plate. We also found that irrespective of the estrous cycle, the behavior of C57BL/6J females was different from that of BALB/cByJ groups in all of the behavioral paradigms. Such strain differences were previously reported in male comparisons, suggesting that the same inter-group differences can be revealed by studying female or male mice. In addition, strain differences were evident even for behaviors that were susceptible to estrous cycle modulations, although their detection might necessitate the constitution of large experimental groups.

Strain and Sex Differences in Anxiety-Like and Social Behaviors in C57BL/6J and BALB/cJ Mice

“…To eliminate the effects of female estrus, only data from diestrous females were analyzed. During the diestrous phase, leukocytes were the predominant type of cell, they were less abundant in the smears than during the metestrous phase, and they were accompanied by a few epithelial nucleated and cornified cells and pleomorphic cells with large dark stained nuclei [32]. Behavioral tests (n=10 for the male group and n=20 for the female group) were performed daily between 14.00-18.00 h and followed a sequence we designed so that the test with the least stress was first.…”

Absence of TI-VAMP/Vamp7 Leads to Increased Anxiety in Mice

“…All experiments were performed in accordance with the European Communities Council Directive of 24 November 1986. Modified SHIRPA, rotarod test, grip test, tail flick, hot plate, open field test, tail suspension, auditory startle reflex reactivity and prepulse inhibition, Y-maze spontaneous alternation task (Meziane et al, 2007;Mandillo et al, 2008), string test (Andrieu et al, 2006), shock threshold test, and Pavlovian fear conditioning (Lamprianou et al, 2006) were previously described. Noninvasive blood pressure was performed in conscious animals by tail cuff sphygmomanometry as described previously (Koutnikova et al, 2009).…”

Effect of Triiodothyronine on Antidepressant Screening Tests in Mice and on Presynaptic 5-HT1A Receptors: Mediation by Thyroid Hormone α Receptors

“…Because experiments with male and female mice were conducted at different time points, direct comparisons between the genders were not possible. In addition, freely cycling female mice were used in the present experiments, and there is evidence in the literature for an effect of the estrous cycle on performance of female mice on various behavioral tests (Meziane et al, 2007). Therefore, results regarding gender differences should be interpreted with reservation.…”