Effect of lethal yellow (AY) mutation and photoperiod alterations on mouse behavior

Abstract

Decrease in natural illumination in fall/winter months causes depressive-like seasonal affective disorders in vulnerable individuals. Obesity is another risk factor of depression. The lethal yellow (A Y ) mutation causes ectopic expression of agouti protein in the brain. Mice heterozygous for A Y mutation (A Y /a) are obese compared to their wild-type littermates (a/a). The main aims of the study were to investigate the effects of A Y mutation, photoperiod and the interaction between these factors on daily activity dynamics, feeding, locomotor and exploratory activities, anxiety-related and depressive-like behaviors in mild stress condition. Six weeks old mouse males of A Y /a and a/a lines were divided into four groups eight animals each and exposed to long-(14 h light and 10 h darkness) or short-(4 h light and 20 h darkness) day conditions for 28 days. Then the behavior of these mice was successively investigated in the home cage, open field, elevated plus-maze and forced swim tests. We did not observed any effect of A Y mutation on the general activity, water and food consumption in the home cage; locomotion and exploration in the open field test; anxiety-related behavior in the open field and elevated plus-maze tests. At the same time, A Y mutation increased depressive-like immobility time in the forced swim test (F 1.28 = 20.03, p = 0.00012). Shortday conditions decreased nocturnal activity in the home cage, as well as locomotion (F 1.28 = 16.33, p = 0.0004) and exploration (F 1.28 = 16.24, p < 0.0004) in the open field test. Moreover, short-day exposition decreased time spent in the center of the open field (F 1.28 = 6.57, p = 0.016) and in the open arms of the elevated plus-maze (F 1.28 = 12.08, p = 0.0017) tests and increased immobility time in the forced swim test (F 1.28 = 9.95, p = 0.0038). However, no effect of the interaction between A Y mutation and photoperiod on immobility time in the forced swim test was observed. Therefore, short-day photoperiod and A Y mutation increased depressive-like behavior in the forced swim test by means of different mechanisms.For citation: Bazhenova E.Y., Fursenko D.V., Khotskin N.V., Sorokin I.E., Kulikov A.V. Effect of lethal yellow (A Y ) mutation and photoperiod alterations on mouse behavior.

Effects of the Combination of the C1473G Mutation in the Tph2 Gene and Lethal Yellow Mutations in the Raly-Agouti Locus on Behavior, Brain 5-HT and Melanocortin Systems in Mice

“…The A Y mutation increases the body mass [ 17 , 23 , 24 ] and depressive-like immobility in the forced swim test [ 24 , 33 , 34 ]. However, this mutation did not affect the brain 5-HT system [ 24 ].…”