Elsevier

Physiology & Behavior

Volume 68, Issues 1–2, 1–15 December 1999, Pages 151-156
Physiology & Behavior

Articles
Lipopolysaccharide facilitates partner preference behaviors in female prairie voles

https://doi.org/10.1016/S0031-9384(99)00154-7Get rights and content

Abstract

Exposure to proinflammatory cytokines (e.g., IL-1β) or lipopolysaccharide (LPS) produces an acute activation of the immune response and results in a repertoire of behavioral patterns collectively termed sickness behaviors. Although nonspecific responses to pathogenic infection have traditionally been viewed as maladaptive effects of infection, sickness behaviors may have significant, adaptive value for the host. One set of adaptive behaviors affected by infection among mammals and birds is mate choice. In Experiment 1, female prairie voles exhibited the expected increase in blood corticosterone concentrations in response to a 0.1 cc i.p. LPS injection (50 μg), indicating activation of the endocrine system. A separate cohort of females was injected with LPS or saline and paired for 6 h with a novel, previously unpaired male. Following the cohabitation period, LPS-injected females spent significantly more time (p < 0.05) with the familiar partner when given a choice between familiar and unfamiliar males in a three-chamber apparatus designed to test partner preferences. Saline-injected females spent significantly more time with the unfamiliar male. In Experiment 2, males injected with LPS or saline spent equal amounts of time with familiar and unfamiliar females following a 6 h cohabitation with a naive female, and therefore, did not exhibit preferences. From a proximate perspective, this study provides evidence that sickness behaviors influence female, but not male, partner preference in prairie voles.

Introduction

Exposure of humans and nonhuman animals to lipopolysaccharide (LPS), a B-cell mitogen, or to pro-inflammatory cytokines [e.g., interleukin-1 (IL-1)] results in a cascade of linked physiological and behavioral responses that are collectively termed sickness behaviors [1]. Typical sickness behaviors include lethargy, anorexia, and reduced exploration, as well as decreased interest in social and reproductive activities [2]. Although nonspecific responses to pathogenic infection, such as anorexia and fever, have traditionally been viewed as maladaptive effects of infection, recent research has suggested that these responses may have significant, adaptive value for the host 1, 2, 3. For example, high body temperature facilitates the destruction of pathogens. Prevention of fever increases the duration of infection, and may induce death [4]. Infected animals often become anemic as well; iron is sequestered away from pathogens that require it for reproduction and treatment of the anemia may prolong the infection [3].

Sickness behavior is also associated with changes in sexual, parental, and other social interactions. Several studies have demonstrated that bacterial infection may either inhibit or facilitate mating 5, 6, 7, 8; however, the proximate mechanism underlying the change in mating behavior among infected animals remain unspecified. IL-1β secretion during an immune response may decrease sexual motivation by reducing sex steroid concentrations. Administration of IL-1β reduces gonadotropin secretion and subsequent sex steroid concentrations 9, 10, 11. However, this neuroendocrine mechanism does not explain instances of enhanced reproduction among infected individuals 12, 13, 14.

On an ultimate level, infection rates and immune responses have been hypothesized to be critical in mate choice. According to one leading hypothesis, females choose mates based on characteristics that serve as general indicators of disease status or parasite load [15]. Infection of the female may also influence mate choice. For example, intracerebroventricular (i.c.v.) administration of IL-β to female rats blocked their normal preference for gonadally intact males over castrated males in a two-choice test [8]. In contrast to females, IL-1β administration does not affect the social preference of male rats. Males prefer intact over castrated females in preference tests, regardless of whether they have been exposed to IL-1β or saline [8]. Additionally, when healthy animals are given a choice between healthy or infected conspecifics, healthy males prefer saline-injected females over infected females in preference tests, whereas healthy females do not distinguish between infected and healthy males [5]. Alternatively, sex differences may exist in sickness behaviors such as lethargy or sexual motivation, and thus obscure mate preferences. Taken together, the immune status of an individual may influence both proximate and ultimate features of reproductive success.

Previous research on sickness behaviors has been conducted on polygynous species such as laboratory rats (Rattus norvegicus) [16] and mice (Mus musculus) [17], in which the males do not contribute to the rearing of offspring. Polygynous individuals rarely develop preferences for their mate. Socially monogamous species must develop a partner preference to form a lasting pair bond. In prairie voles (Microtus ochrogaster), partner preference develops after a few hours in either sexual or nonsexual cohabitation with an opposite sex conspecific 18, 19, 20, 21, 22. Reproductive behavior in monogamous prairie voles, in general, tends to be strongly influenced by intrinsic variables such as hormones, and extrinsic variables such as social factors [18]. Activation of the immune system alters hormones and may influence partner preference expression in male and female prairie voles. High corticosterone concentrations disrupt partner preference in female prairie voles and facilitate partner preference in male prairie voles [18]. Exposure to either IL-1β or LPS significantly elevates adrenocorticotropic hormone (ACTH) and corticosterone concentrations in rats and mice 23, 24. While LPS has no direct effect on ACTH production or adrenal output in rats and mice, the release of cytokines stimulates the release of corticotropin releasing hormone (CRH) from the hypothalamus, and the subsequent release of ACTH from the pituitary [25].

The goal of this study was to determine the effects of LPS administration on the formation and expression of social preferences in both male and female prairie voles. Male prairie voles significantly increase corticosterone concentrations in response to LPS [10]. Previously untested, we hypothesized that LPS would elevate corticosterone concentrations in female prairie voles. Elevated blood corticosterone concentrations should impair partner preference formation following a 6-h period of cohabitation in females, but either enhance or not alter partner preference in male prairie voles.

Section snippets

Animals

Sixteen female and 14 male prairie voles (Microtus ochrogaster) obtained from stock originally trapped near Urbana, IL, were used in partner preference tests. An additional 12 females were used to determine blood corticosterone concentrations following treatment. All animals were adults between 60 days and 1 year of age, with a mean weight of 40 g. Animals were individually housed at least 2 weeks prior to the beginning of the experiment in polypropylene cages (27.8 × 7.5 × 13 cm) in colony

Cohabitation

During the final 3 h of the 6-h cohabitation period, females injected with LPS spent significantly more of the total time in contact with the cohabitation partner than saline injected females, t(12) = 2.19, p < 0.05 (Fig. 1A).

Partner preference

Female prairie voles injected with LPS spent significantly more time with familiar partners than unfamiliar animals, t(14) = 3.552, p < 0.003 (Fig. 1B). LPS-injected females also spent more time with familiar partners than saline injected females, t(14) = −2.776, p <

Discussion

LPS administration in female prairie voles facilitated pair bonding and partner-preference expression. We initially hypothesized that the effects of LPS on partner preference may be mediated by changes in corticosterone concentrations. Infected female prairie voles exhibited the expected increase in blood corticosterone concentrations, but spent significantly more time with the familiar partner than the unfamiliar animal. In contrast, healthy females spent significantly more time with the

Acknowledgements

The authors thank Josh Pahys and Susan Mozzicato for assistance with cohabitation and preference test video scoring. This research was supported by NIMH Grant MH 57535 and NSF Grant IBN 97-23420.

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    Current address: Department of Immunology and Molecular Microbiology, Johns Hopkins University, School of Hygiene and Public Health, Baltimore, MD 21205.

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