The influence of photoperiod and sex on lipopolysaccharide-induced hypoactivity and behavioral tolerance development in meadow voles (Microtus pennsylvanicus)

Lipopolysaccharide (LPS), the minimal immunogenic component of Gram-negative bacteria, is released during infection and causes a variety of sickness behaviors including decreased locomotor activity. This study considered how photoperiod and sex influence the effects of LPS in the meadow vole, Microtus pennsylvanicus. Male and female voles were housed under either reproductively stimulatory (long day: 16 h) or inhibitory (short day: 8 h) photoperiods. On Days 1 and 8, voles were injected with LPS (200 μg/kg, i.p.) or saline vehicle and locomotor activity was assessed 2 h later in an automated open field for 1 h. The first exposure to LPS caused significant decrements in locomotor activity in all LPS-treated groups, regardless of photoperiod or sex. On Day 8, both short day males and females exhibited behavioral tolerance to LPS, no longer displaying significant activity decrements. In contrast, long day females reinjected with LPS on Day 8 still exhibited significant hypoactivity on all locomotor measures. Similarly, long day males also appeared to exhibit a sustained expression of sickness behaviors on Day 8. In long day females, higher circulating progesterone levels were associated with an attenuated rate of tolerance formation to LPS. The present findings support the winter immunoenhancement hypothesis, which states that small mammals which undergo severe seasonal fluctuations undergo compromised immune functioning during the breeding season, and further indicate a potential role for progesterone in modulating these seasonal immune fluctuations in females.