Anti-inflammatory agents attenuate the passive responses of guinea pig pups: Evidence for stress-induced sickness behavior during maternal separation

Abstract

A previous study found that intracerebroventricular (ICV) infusion of 25 μg of α-MSH reduced the passive responses (crouched stance, eye-closing, piloerection) of guinea pig pups during a 3-hr isolation in a novel environment. Because α-MSH has broad anti-inflammatory properties, the results suggested that proinflammatory factors play a role in mediating the behavior of isolated infants. The present study further investigated this possibility. In Experiment 1, injection of lipopolysacchride (LPS) increased the number of 60-s intervals in which pups expressed the same three responses during a 1-hr test, and ICV infusion of α-MSH significantly reduced the effect of LPS on crouching and piloerection. In Experiment 2, the prostaglandin synthesis inhibitor indomethacin (10mg/kg) reduced the number of 60-s intervals in which pups exhibited both crouching and the full suite of passive responses during a 3-hr isolation in a novel environment. Together these results provide further support for the hypothesis that the passive behaviors exhibited during prolonged isolation are "stressinduced sickness behaviors" mediated by proinflammatory factors. Keywords sickness behaviors; acute phase response; inflammation; maternal separation; isolation; guinea pig Stimulation of the innate immune system results in a systemic physiological and behavioral reaction known as the acute phase response or sickness (Baumann & Gauldie, 1994). Components of the acute phase response include: fever, shifts in the synthesis of liver proteins, activation of the hypothalamic-pituitary-adrenal system, sleepiness, assumption of a curled or hunched posture, piloerection, shivering, and reductions in various activities. Though the behavioral components may appear to be simply the result of debilitation, they are adaptive responses that contribute to recuperation by, for instance, supporting the production of fever (e.g., hunched posture, piloerection, shivering), which in turn, can inhibit further proliferation of pathogens (Aubert, 1999;Hart, 1988). The acute phase response is triggered by the release of proinflammatory cytokines (e.g., IL-1, IL-6, TNF-α) in the periphery and CNS (Dantzer, 2004).Address correspondence to: Michael B. Hennessy, PhD, Department of Psychology, 335 Fawcett Hall, Wright State University, 3640 Col Glenn Hwy, Dayton, OH 45435, 937.775.2943 (voice), 937.775.3347 (FAX), michael.hennessy@wright.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. In the last decade, it has become apparent that aspects of the acute phase response, including sickness behaviors, do not occur solely ...

Naproxen attenuates sensitization of depressive-like behavior and fever during maternal separation

“…The sensitization of passive behavior was accompanied by a sensitization of fever, an indirect measure of proinflammatory activity, though in the second experiment only the NAP group showed this effect. Our results also extend previous findings that other anti-inflammatory agents (indomethacin, IL-10, and α-MSH) attenuate depressive-like behavior during separations immediately following drug administration [36, 37, 38], and that IL-10 can abolish sensitization of depressive-like behavior during a second separation the following day [40]. …”

“…The reduction of the passive, depressive-like response in guinea pigs receiving naproxen indicates prostaglandin involvement in the behavioral effect as well. Our earlier study with the COX inhibitor indomethacin [36] provided evidence for prostaglandin mediation of depressive-like behavior during an initial separation experience. The current results both support this conclusion and point to prostaglandin mediation of the sensitization of the depressive-like behavior with repeated separation.…”

“…These stages are reminiscent of the “protest” and “despair” of separated macaques [32], though the transition to the second stage develops over the course of hours rather than days. Several sets of findings indicate that this second stage of responsiveness in guinea pigs is mediated by inflammatory processes: (1) direct activation of an inflammatory reaction with lipopolysaccharide hastens the onset of the passive stage [33]; (2) separation elicits physiological signs of an inflammatory reaction, specifically fever and increased proinflammatory cytokine expression [34, 35]; and, (3) three different anti-inflammatory agents (including the COX inhibitor indomethacin) reduce the passive response to separation [36, 37, 38]. …”

Prenatal Lipopolysaccharide Exposure Affects Maternal Behavior and Male Offspring Sexual Behavior in Adulthood

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Early Life Experiences Affect Adult Delayed-Type Hypersensitivity in Short and Long Photoperiods

“…Stress can cause epigenetic changes in the immune system (Uddin et al, 2010), suggesting that immune cells may be programmed during early life to respond differentially to an immune challenge. Moreover, maternal separation may cause increased inflammation in infancy (Hennessy et al, 2007), and inflammation during early development impacts immune function in adulthood (Kentner et al, 2010).…”