Sensitization of depressive-like behavior during repeated maternal separation is associated with more-rapid increase in core body temperature and reduced plasma cortisol levels

Abstract

Infant guinea pigs exhibit a 2-stage response to maternal separation: an initial active stage, characterized by vocalizing, and a second passive stage marked by depressive-like behavior (hunched posture, prolonged eye-closure, extensive piloerection) that appears to be mediated by proinflammatory activity. Recently we found that pups showed an enhanced (i.e., sensitized) depressive-like behavioral response during repeated separation. Further, core body temperature was higher during the beginning of a second separation compared to the first, suggesting a more-rapid stress-induced febrile response to separation the second day, though the possibility that temperature was already elevated prior to the second separation could not be ruled out. Therefore, the present study examined temperature prior to, and during, 2 daily separations. We also examined the temperature response to a third separation conducted 3 days after the second, and assessed the effect of repeated separation on plasma cortisol levels. Core temperature did not differ just prior to the separations, but showed a more-rapid increase and then decline during both a second and third separation than during a first. Temperature responses were not associated with changes in motor activity. Depressive-like behavior was greater during the second and third separations. Pups separated a first time showed a larger plasma cortisol response at the conclusion of separation than did animals of the same age separated a third time. In all, the results indicate that the sensitization of depressive-like behavior during repeated separations over several days is accompanied by a more-rapid febrile response that may be related to a reduction of glucocorticoid suppression.

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

“…In agreement with several recent reports [35, 41], we found that the passive depressive-like response of guinea pigs showed sensitization with repeated separation. The active behavior of vocalizing did not sensitize, but rather declined, an effect previously demonstrated to be due to increased age rather than habituation [35, 41].…”

“…The active behavior of vocalizing did not sensitize, but rather declined, an effect previously demonstrated to be due to increased age rather than habituation [35, 41]. 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.…”

“…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]. …”

Filial attachment and its disruption: Insights from the guinea pig

“…Even a single 3-hr separation increases the level of passive, but not active, behaviors observed during separation the following day (Schneider et al, 2012). If 3-week-old pups are then separated a third time 4 or 10 days after the first separation, the same heightened level of passive behavior is observed (Hennessy, Paik, Caraway, Schiml, & Deak, 2011;Schneider et al, 2012;Yusko, Hawk, Schiml, Deak, & Hennessy, 2012;Fig. 2).…”

“…2). These increases are not associated with increases in locomotor activity, and neither the behavioral nor the core temperature change can be accounted for by the increasing age of the animals (Schneider et al, 2012; Yusko et al, 2012). The sensitization of the fever response implies a sensitization of inflammatory mechanisms, though this remains to be directly tested.…”