Early Attachment Disruption, Inflammation, and Vulnerability for Depression in Rodent and Primate Models

Early experiments in nonhuman primates established the relation between disruption of filial attachment and depressive-like outcomes. Subsequent studies in rats and mice have been instrumental in linking depressive-like outcomes to disturbances in maternal behavior. Another aspect of attachment disruption, absence of the attachment object per se, may be studied more effectively in a different laboratory rodent—the guinea pig. Here, we discuss the rationale for using guinea pigs for this work. We then review guinea pig studies providing evidence for inflammatory mechanisms mediating both depressive-like behavior during separation as well as sensitization of stress responsiveness such as is thought to lead to increased vulnerability to depression at later ages. Finally, we discuss recent complementary work in adult monkeys that suggests cross-species generalizability of broad principles derived from the guinea pig experiments. Overall, the findings provide experimental support for human research implicating inflammatory mechanisms in the development of increased stress responsiveness and vulnerability to depression following attachment disruption and other forms of early-life stress. Specifically, the findings suggest inflammatory mechanisms may set in motion a cascade of underlying processes that mediate later increased stress responsiveness and, therefore, depression susceptibility

Effects of Gonadotropin-Releasing Hormones, Corticotropin-Releasing Hormone, and Vasopressin on Female Sexual Behavior

The effects of intracerebroventricular (icv) infusion of four neuropeptides on female sexual behavior were examined in the female musk shrew (Suncus murinus). In the first experiment, (icv) infusion of 100 ng of the mammalian form of gonadotropin-releasing hormone (mGnRH) facilitated rapid display of receptivity. Gonadotropin-releasing hormone-infused females had shorter latencies to rump present and tail wag, compared with controls. In a second experiment, icv administration of the other form of GnRH present in musk shrew brain, the chicken GnRH-II form, produced no changes in female behavior relative to the control condition. In Experiment 3, icv delivery of corticotropin-releasing hormone (CRH) facilitated female sexual behavior, relative to vasopressin and controls. The females treated with CRH had shorter latencies to display rump present, tail wag, and for the receipt of the first missed intromission compared with females in the other treatment groups. Vasopressin increased female scent marking relative to that of CRH-treated females. These data indicate that neurohormones of the hypothalamic–pituitary–gonadal and the hypothalamic–pituitary–adrenal axes can facilitate reproductive behavior in S. murinus

Cortisol Facilitates Induction of Sexual Behavior in the Female Musk Shrew (Suncus murinus)

The role of cortisol in sexual behavior in the female musk shrew (Suncus murinus) was examined. High levels of cortisol were associated with sexual receptivity, as indicated by species-typical tail-wagging behavior, during brief(15-min) mating tests. When cortisol production was blocked by metyrapone, an 11-β-hydroxylase inhibitor, females exhibited reduced sexual behavior relative to controls, an effect that was reversed with acute cortisol replacement. These results indicate that cortisol facilitates, rather than inhibits, sexual behavior in this species and expands the comparative understanding of hypothalamic–pituitary–adrenal (HPA) effects on reproduction

Cortisol Facilitates Induction of Sexual Behavior in the Female Musk Shrew (Suncus murinus)

The role of cortisol in sexual behavior in the female musk shrew (Suncus murinus) was examined. High levels of cortisol were associated with sexual receptivity, as indicated by species-typical tail-wagging behavior, during brief(15-min) mating tests. When cortisol production was blocked by metyrapone, an 11-β-hydroxylase inhibitor, females exhibited reduced sexual behavior relative to controls, an effect that was reversed with acute cortisol replacement. These results indicate that cortisol facilitates, rather than inhibits, sexual behavior in this species and expands the comparative understanding of hypothalamic–pituitary–adrenal (HPA) effects on reproduction

Effects of Gonadotropin-Releasing Hormones, Corticotropin-Releasing Hormone, and Vasopressin on Female Sexual Behavior

The effects of intracerebroventricular (icv) infusion of four neuropeptides on female sexual behavior were examined in the female musk shrew (Suncus murinus). In the first experiment, (icv) infusion of 100 ng of the mammalian form of gonadotropin-releasing hormone (mGnRH) facilitated rapid display of receptivity. Gonadotropin-releasing hormone-infused females had shorter latencies to rump present and tail wag, compared with controls. In a second experiment, icv administration of the other form of GnRH present in musk shrew brain, the chicken GnRH-II form, produced no changes in female behavior relative to the control condition. In Experiment 3, icv delivery of corticotropin-releasing hormone (CRH) facilitated female sexual behavior, relative to vasopressin and controls. The females treated with CRH had shorter latencies to display rump present, tail wag, and for the receipt of the first missed intromission compared with females in the other treatment groups. Vasopressin increased female scent marking relative to that of CRH-treated females. These data indicate that neurohormones of the hypothalamic–pituitary–gonadal and the hypothalamic–pituitary–adrenal axes can facilitate reproductive behavior in S. murinus

Light–Dark Variation and Changes Across the Lactational Period in the Behaviors of Undisturbed Mother and Infant Guinea Pigs (\u3cem\u3eCavia porcellus\u3c/em\u3e)

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

Light–Dark Variation and Changes Across the Lactational Period in the Behaviors of Undisturbed Mother and Infant Guinea Pigs (\u3cem\u3eCavia porcellus\u3c/em\u3e)

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

Sociality and Sickness: Have Cytokines Evolved to Serve Social Functions Beyond Times of Pathogen Exposure?

During pathogen exposure or some forms of stress, proinflammatory processes induce an array of motivated and behavioral adjustments termed “sickness behaviors”. Although withdrawal from social interactions is a commonly observed sickness behavior, the relation between social behavior and sickness is much more complex. Sickness can suppress or stimulate social behavior. Sickness can serve as a social cue. Stressors that are social in nature can induce sickness behaviors, and sickness behavior can be readily suppressed by meaningful social stimuli. The nature, context, and timing of these effects together suggest that cytokine-induced behavior may play a role in mediating social interactions in various non-pathological conditions

Sociality and Sickness: Have Cytokines Evolved to Serve Social Functions Beyond Times of Pathogen Exposure?

During pathogen exposure or some forms of stress, proinflammatory processes induce an array of motivated and behavioral adjustments termed “sickness behaviors”. Although withdrawal from social interactions is a commonly observed sickness behavior, the relation between social behavior and sickness is much more complex. Sickness can suppress or stimulate social behavior. Sickness can serve as a social cue. Stressors that are social in nature can induce sickness behaviors, and sickness behavior can be readily suppressed by meaningful social stimuli. The nature, context, and timing of these effects together suggest that cytokine-induced behavior may play a role in mediating social interactions in various non-pathological conditions

Stress-Induced Sickness Behaviors: An Alternative Hypothesis for Responses During Maternal Separation

During maternal separation, some primate and nonprimate species show a biphasic (active/passive) response. The second stage is characterized by reduced activity, a hunched body posture, and other behaviors. Traditionally, the second stage has been referred to as “despair” and is considered an animal model for human depression. Recent research in psychoneuroimmunology suggests an alternative hypothesis—that behaviors occurring during the second passive phase represent stress-induced “sickness behaviors.” This perspective more readily accounts for findings in widely divergent species, does not require assumptions regarding the ability to express complex emotional states, is empirically testable, and aligns the separation model with recent hypotheses regarding the nature and ontogeny of depressive illness. © 2001 John Wiley & Sons, Inc. Dev Psychobiol 39: 76–83, 200