Short photoperiods attenuate central responses to an inflammogen Laura K. Fonken a,⇑ , Tracy A. Bedrosian a , Heather D. Michaels b , Zachary M. Weil a , Randy J. Nelson a a Department of Neuroscience and Institute for Behavioral Medicine Research, The Ohio State University Medical Center, Columbus, OH 43210, USA b Department of Psychology, Harvard University, Cambridge, MA 02138, USA article info Article history: Received 28 November 2011 Received in revised form 24 January 2012 Accepted 25 January 2012 Available online 2 February 2012 Keywords: Fever Anhedonia Seasonality Sickness behavior Immune Siberian hamster Phodopus sungorus abstract In most parts of the world, environmental conditions vary in a predictable seasonal manner. Thus, sea- sonal variation in reproductive timing and immune function has emerged in some species to cope with disparate seasonal demands. During the long days of spring and summer when food availability is high and thermoregulatory demands low, Siberian hamsters invest in reproduction, whereas during the harsh short days of winter hamsters divert energy away from reproductive activities and modify immune capa- bilities. Many seasonal adaptations can be recapitulated in a laboratory setting by adjusting day length (photoperiod). Early-life photoperiods are important sources of seasonal information and can establish an individual’s developmental trajectory. Siberian hamsters housed under short days (SD; 8 h light/ day) recover more rapidly than long-day (LD; 16 h light/day) hamsters from immune activation with lipopolysaccharide (LPS). SD hamsters attenuate fever response, reduce cytokine production, and abro- gate behavioral responses following LPS injection. The mechanism by which SD Siberian hamsters atten- uate febrile response remains unspecified. It is possible that periphery-to-brain communication of inflammatory signals is altered by exposure to photoperiod. Rather than testing photoperiod effects on each of the multiple routes by which immunological cues are communicated to the CNS, we administered LPS intracerebroventricularly (i.c.v.) following adolescent exposure to either 6 weeks of SD or LD. Injec- tion of LPS i.c.v. led to a similar immune reaction in SD hamsters as previously reported with intraperi- toneal injection. Short days attenuated the response to LPS with diminished fever spike and duration, as well as decreased locomotor inactivity. Furthermore, only LD hamsters demonstrated anhedonic-like behavior following LPS injection as evaluated by decreased preference for a milk solution. These results suggest that photoperiodic differences in response to infection are due in part to changes in central immune activation. Ó 2012 Elsevier Inc. All rights reserved. 1. Introduction Many non-tropical animals display annual variation in reproduc- tive and immune activity. Winter represents an energetic bottle- neck during which increased thermoregulatory requirements coincide with reduced energy availability (Martin et al., 2008). Dur- ing the spring and summer, which encompasses much of the breed- ing season for small, nontropical vertebrates, investments are biased towards reproductive activities; however, during late au- tumn and winter, energy is reallocated to mechanisms promoting over-winter survival. Short day lengths (SD; <12.5 h light/day) inhi- bit reproductive function, and alter several aspects of immune func- tion in some seasonally breeding rodents (Bilbo et al., 2002a; Demas et al., 1996; Goldman, 2001; Navara et al., 2007; Prendergast et al., 2003a,b, 2007a; Weil et al., 2006a). Inflammatory responses, in par- ticular, are modulated by photoperiod (Bilbo et al., 2002b; Fenn et al., 2011; Prendergast et al., 2003a; Pyter et al., 2005). One espe- cially well-characterized short-day effect on immune function is that adult Siberian hamsters (Phodopus sungorus) recover faster than long-day hamsters from immune activation to lipopolysaccha- ride (LPS; a component of gram negative bacterial cell walls that activates the immune system; AKA endotoxin) (Bilbo et al., 2002b). Because environmental conditions vary in a predictable sea- sonal manner over most of the planet, the external conditions experienced during early development differ among individuals born at different times of the year. Siberian hamsters use photope- riod information early in life, as well as in adulthood to establish somatic and behavioral developmental trajectory (Pyter and Nelson, 2006; Weil et al., 2006b). Although much of the research on photoperiod effects on immune function is based on adults, early-life photoperiod is an important source of seasonal informa- tion (Prendergast et al., 2004a; Pyter and Nelson, 2006; Weil et al., 2006b). Because the adaptations associated with investing in reproduction or survival mechanisms are generally mutually exclusive, it is critical for small animals to respond appropriately to seasonal cues soon after birth. 0889-1591/$ - see front matter Ó 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.bbi.2012.01.017 ⇑ Corresponding author. Address: Department of Neuroscience, The Ohio State University, 740 Biomedical Research Tower, 1339 W 12th Avenue, Columbus, OH 43210, USA. Tel.: +1 614 688 4674. E-mail address: fonken.1@osu.edu (L.K. Fonken). Brain, Behavior, and Immunity 26 (2012) 617–622 Contents lists available at SciVerse ScienceDirect Brain, Behavior, and Immunity journal homepage: www.elsevier.com/locate/ybrbi