Michael B. Hennessy

Human interaction moderates plasma cortisol and behavioral responses of dogs to shelter housing

Housing in an animal shelter is a stressful experience for dogs. This study examined the effects of different forms of human interaction on concentrations of circulating cortisol and stress-related behaviors of dogs within 40 h of admittance to a county animal shelter. Blood samples were collected before and after 30-min sessions in a secluded area in which dogs received one of three forms of human interaction: exposure to a passive human, petting, or play. Controls were either exposed to the secluded area alone, or remained in the general housing area. There was a substantial and near uniform reduction in plasma cortisol concentrations from pretest to post-test in all three conditions receiving human interaction, but not in control conditions. Human interaction also reduced behavioral signs of excitation/social solicitation (vocalizing) and fear (panting). Finally, pretest cortisol levels were found to predict levels of panting and another fear-related behavior (tongue protrusions) that dogs exhibited during subsequent testing. The findings suggest practical means of reducing stress, and potentially of improving the welfare, of dogs in shelters.

Early Attachment-Figure Separation and Increased Risk for Later Depression: Potential Mediation by Proinflammatory Processes

Early maternal separation and other disruptions of attachment relations are known to increase risk for the later onset of depressive illness in vulnerable individuals. It is suggested here that sensitization involving proinflammatory processes may contribute to this effect. This argument is based on: (1) current notions of the role of proinflammatory cytokines in depressive illness; (2) evidence that proinflammatory cytokines mediate depressive-like behavior during separation in a rodent model of infant attachment; and (3) comparisons of the effects of early proinflammatory activation versus maternal separation on later proinflammatory activity and biobehavioral processes related to depression. The possible interaction of proinflammatory processes and corticotropin-releasing factor in the sensitization process is discussed.

Anti-Inflammatory Influences on Behavioral, but not Cortisol, Responses during Maternal Separation

The present study examined the effect of anti-inflammatory agents on the behavioral and plasma cortisol responses of guinea pig pups during isolation in a novel environment. In Experiment 1, intracerebroventricular (i.c.v.) administration of interleukin-10 (IL-10), across a range of doses, significantly reduced passive behaviors of isolated pups. In Experiment 2, neither i.c.v. IL-10 nor alpha-melanocyte stimulating hormone affected the plasma cortisol response to the separation procedure. These results provide further evidence that the passive behaviors of isolated guinea pig pups are mediated by proinflammatory cytokines and indicate that cytokines do not affect behavior indirectly by means of an action on hypothalamic-pituitary-adrenal activity.

Light-dark variation and changes across the lactational period in the behaviors of undisturbed mother and infant guinea pigs (Cavia porcellus).

Lactating guinea pigs (Cavia porcellus) and their litters were observed by videophotography across the light/dark cycle at 1, 11, 21, and 31 days postpartum. The highest level of behavioral activity was seen in the dark, particularly in the hour after light offset. This circadian pattern was evident from Day 1 in mothers and from Day 11 in pups. Contact between mothers and pups was inversely related to activity, occurring more frequently during light. Maternal grooming of pups occurred on Day 1 and then declined: self-grooming by pups increased across days. Intake of solid food and water by pups occurred on Day 1 and increased thereafter. A nearly complete transition from nursing to independent ingestion was observed between 21-31 days of age. Overall, we document several ontogenetic changes in young guinea pigs and demonstrate that under laboratory conditions mother and infant guinea pigs exhibit a nocturnal activity pattern.

Proinflammatory Activity and the Sensitization of Depressive-Like Behavior during Maternal Separation

When guinea pig pups are isolated for a few hours in a novel environment, they exhibit a distinctive passive behavioral response that appears to be mediated by proinflammatory activity. Recently, we observed that pups separated on two consecutive days show an enhanced (sensitized) passive response on the second day. In Experiment 1, pups receiving intracerebroventricular infusion of 50 ng of the anti-inflammatory cytokine interleukin-10 prior to a first separation failed to show a sensitized behavioral response to separation the next day. In Experiment 2, pups separated on Days 1 and 2, or just 2, showed an increase in passive responding during separation on Day 5. Pups injected with the bacterial antigen lipopolysacchride (LPS; 75 μg/kg body weight, intraperitoneal) prior to separation on Day 1 showed an increase in passive behavior several days later not shown by pups injected with saline prior to Day 1 separation. However, injection of LPS without separation on the first day did not enhance responding during an initial separation on the second day. These results suggest that immune activation is necessary, but not sufficient, to account for the sensitization of passive behavior of isolated guinea pig pups the following day, that boosting proinflammatory activity during an initial separation may promote sensitization several days later, and that the sensitized response persists for at least several days.

Separation, Sickness, and Depression A New Perspective on an Old Animal Model

Studies of prolonged separation from the attachment figure that were conducted with infant monkeys during the middle of the 20th century identified a passive behavioral response, termed “despair,” that appeared to model human depressive illness. Studies in guinea pigs, which exhibit filial attachment that resembles attachment in monkeys, have described a similar passive response to briefer periods of maternal separation. Recent evidence indicates that elements of the immune system mediate the passive behavioral response of guinea pigs. These findings accord well with current ideas that immune responses contribute to depressive illness, suggest new hypotheses about how maternal separation might promote depression, and give us a rodent model in which such hypotheses might be tested.

Naproxen Attenuates Sensitization of Depressive-Like Behavior and Fever during Maternal Separation

Early life stress can increase susceptibility for later development of depressive illness though a process thought to involve inflammatory mediators. Isolated guinea pig pups exhibit a passive, depressive-like behavioral response and fever that appear mediated by proinflammatory activity, and which sensitize with repeated separations. Treatment with an anti-inflammatory can attenuate the behavioral response during the initial separation and separation the following day. Here we used the cyclooxygenase inhibitor naproxen to examine the role of prostaglandins in mediating the depressive-like behavior and core body temperature of young guinea pigs during an initial separation, separation the next day, and separation 10 days after the first. The passive, depressive-like behavior as well as fever sensitized with repeated separation. Three days of injection with 14 mg/kg of naproxen prior to the initial separation reduced depressive-like behavior during all three separations. A 28 mg/kg dose of naproxen, however, had minimal effect on behavior. Fever during the early separations was moderated by naproxen, but only at the higher dose. These results suggest a role of prostaglandins in the behavioral and febrile response to maternal separation, and particularly in the sensitization of depressive-like behavior following repeated separation.

Maternal Separation Increases Later Immobility During Forced Swim in Guinea Pig Pups: Evidence for Sensitization of a Depressive-Like State

Early-life stress is thought to increase later vulnerability for developing depressive illness by sensitizing underlying stress-responsive systems. Guinea pig pups separated from their mother and isolated in a novel cage for 3 hr exhibit a sensitized depressive-like behavioral response when separated again the following day as well as weeks later. The behavioral response and its sensitization appear to be mediated by inflammatory factors. To determine if this sensitization is specific to the separation response or if it reflects a broader underlying depressive-like state, guinea pig pups that had either been separated for 3 hr or remained with their mothers were observed in the forced swim test the following 3 days. Earlier separation was found to increase the duration of immobility, a measure sensitive to antidepressant treatment. These results support the use of the guinea pig as a model for examining mechanisms of inflammatory-mediated sensitization of depression following stress in early life.

Increases in the circulating testosterone of maturing male guinea pigs appear neither necessary nor sufficient for heightened maternally directed sexual and social/courtship behavior.

Periadolescent male guinea pigs housed continuously with their mother since birth exhibit little maternally directed sexual behavior. However, if rehoused apart from the mother for 24 h, they show elevations in circulating testosterone concentrations and display frequent sexual responses and increased social/courtship behavior upon reunion with her. We investigated the role of testosterone in the disinhibition of maternally directed sexual and social/courtship behavior. Subcutaneous implants of testosterone (Experiment 1) did not trigger maternally directed sexual behavior or an increase in social/courtship behavior among males housed continuously with their mothers. Further, neither blocking androgen receptors (Experiment 2) nor preventing the surge in testosterone (Experiment 3) prevented males housed without the mother from exhibiting increased maternally directed sexual and social/courtship behavior upon reunion. These findings indicate that the increase in testosterone that males exhibit when rehoused apart from the mother is neither sufficient nor necessary for the disinhibition of maternally directed sexual and social/courtship behavior observed when mother and son are reunited.