Depressive behaviors and decreased expression of serotonin reuptake transporter in rats that experienced neonatal maternal separation

Lee, Jong-Ho; Kim, Hyung Jin; Kim, Jae Goo; Ryu, Vitaly; Kim, Bom-Taeck; Kang, Dong Won; Jahng, Jeong Won

doi:10.1016/j.neures.2007.01.008

Cited by 201 publications

(137 citation statements)

References 46 publications

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“…Previous studies have reported that experiences of maternal separation during pre-weaning period (MS) increase the hypothalamic NPY level in rats later in life (Jimenez-Vasquez et al, 2001;Husum and Mathe, 2002), and that the hypothalamic NPY expression is dis-regulated in MS rats in relation with the HPA axis dysfunction Ryu et al, 2008). We have previously reported that our MS offspring shows anxiety-and depression-like behaviors later in life (Lee et al, 2007) and develops a binge-like eating behavior with increased expression of the hypothalamic NPY when they are challenged with repeated fasting/refeeding cycles, a typical diet trial in human (Ryu et al, 2008). It has been reported that symptoms of anxiety and depression are associated with the pathophysiology of eating disorders (Goossens et al, 2009; see for review), especially with binge-like eating disorders (Grilo et al, 2009;Javaras et al, 2008).…”

Section: Introductionmentioning

confidence: 72%

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The arcuate NPY, POMC, and CART expressions responding to food deprivation are exaggerated in young female rats that experienced neonatal maternal separation

et al. 2011

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Section: Introductionmentioning

confidence: 72%

“…The incidence of eating disorders is known to be higher in females than in males. Although we have previously demonstrated that our MS rats can be used as an animal model system to study the pathophysiology of eating disorders, results were all limited to males Lee et al, 2007;Ryu et al, 2008;Jahng et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

The arcuate NPY, POMC, and CART expressions responding to food deprivation are exaggerated in young female rats that experienced neonatal maternal separation

et al. 2011

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“…Early postnatal life constitutes a critical period during which alterations in 5-HT impact adult emotional behavior, suggesting that 5-HT plays a key role in the development of brain circuits that modulate adult emotionality (43)(44)(45)(46)(47). Indeed, atypical infant increases in 5-HT induced by chronic fluoxetine (FLX) exposure, 5-HT transporter knockout, or disruptions in maternal care, result in long-term changes in 5-HT and contribute to later-life depression-like symptoms (11,(44)(45)(46)48). Third, learned safety signals exert protective effects on animal models of depression comparable with those obtained by adult antidepressant treatment (36), suggesting that serotonergic mechanisms contribute to these repair effects.…”

Section: Significancementioning

confidence: 99%

“…Long-lasting effects of infant trauma relevant to depression include disruptions in social behavior, alterations in the serotonin (5-HT) system, and amygdala dysfunction (2,(5)(6)(7)(8), which have been replicated by animal models (9)(10)(11)(12)(13)(14)(15). Paradoxically, trauma-linked cues-even those associated with abusive attachment-can elicit strong attraction and feelings of comfort in humans (16,17).…”

mentioning

confidence: 99%

Enduring good memories of infant trauma: Rescue of adult neurobehavioral deficits via amygdala serotonin and corticosterone interaction

Rincón-Cortés

Barr

Mouly

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Children form a strong attachment to their caregiver-even when that caretaker is abusive. Paradoxically, despite the trauma experienced within this relationship, the child develops a preference for trauma-linked cues-a phenomenon known as trauma bonding. Although infant trauma compromises neurobehavioral development, the mechanisms underlying the interaction between infant trauma bonding (i.e., learned preference for trauma cues) and the long-term effects of trauma (i.e., depressive-like behavior, amygdala dysfunction) are unknown. We modeled infant trauma bonding by using odor-shock conditioning in rat pups, which engages the attachment system and produces a life-long preference for the odor that was paired with shock. In adulthood, this trauma-linked odor rescues depressive-like behavior and amygdala dysfunction, reduces corticosterone (CORT) levels, and exerts repair-related changes at the molecular level. Amygdala microarray after rescue implicates serotonin (5-HT) and glucocorticoids (GCs), and a causal role was verified through microinfusions. Blocking amygdala 5-HT eliminates the rescue effect; increasing amygdala 5-HT and blocking systemic CORT mimics it. Our findings suggest that infant trauma cues share properties with antidepressants and safety signals and provide insight into mechanisms by which infant trauma memories remain powerful throughout life.E arly-life trauma is associated with compromised neurobehavioral development and vulnerability to later-life psychiatric disorders like depression (1-5). Long-lasting effects of infant trauma relevant to depression include disruptions in social behavior, alterations in the serotonin (5-HT) system, and amygdala dysfunction (2, 5-8), which have been replicated by animal models (9-15). Paradoxically, trauma-linked cues-even those associated with abusive attachment-can elicit strong attraction and feelings of comfort in humans (16,17). Furthermore, a lifelong attraction to trauma-linked cues has also been demonstrated in rodent models of infant trauma, which suggests that sensory cues learned during infancy alter adult behaviors and amygdala activity (12,18,19).To explore the enduring effects of infant trauma and the mechanisms underlying their modulation by infant trauma-linked cues, we used an odor-learning paradigm during the sensitive period for attachment learning in rat pups, postnatal (PN) days 8-12, which is characterized by rapid and robust odor-preference learning that extends to aversive stimuli (14,(20)(21)(22). Specifically, we used infant olfactory classical conditioning in which a novel peppermint odor is paired with a mild shock (0.5 mA, 1s) to produce a preferred odor that functions behaviorally as a maternal odor and results in neural activation comparable with that induced by natural maternal odor (20,(23)(24)(25). During the sensitive period, low endogenous levels of corticosterone (CORT) and attenuated shock-induced CORT release prevent the infant amygdala from exhibiting the learning-induced plasticity required for avoidance learning (1...

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“…22 Rats that experienced neonatal MS also showed depression-and anxiety-like behaviors with alterations in the brain serotonergic system. 23 Patients with eating disorders often exhibit symptoms of depression and/or anxiety, and serotonergic dysfunctions have been suggested to be implicated in the pathophysiology of eating disorders. 24,25 These data suggest that our model of neonatal MS could be useful in defining the pathophysiologic mechanism underlying eating disorders.…”

Section: Introductionmentioning

confidence: 99%

Sustained hyperphagia in adolescent rats that experienced neonatal maternal separation

et al. 2008

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Objective: To examine the neurobiological basis of bingeing-related eating disorders using an animal model system. Design: Sprague-Dawley pups were separated from dam for 3 h daily during the first two weeks of birth (maternal separation (MS)), or left undisturbed (non-handled (NH)). Pups were subjected to repeated fasting/refeeding (RF) cycles; that is, 24 h food deprivation and 24 h RF (NH/RF or MS/RF), or had free access to food and water (NH/fed control (FC) or MS/FC) from postnatal day (PND) 28-40. Measurements: Body weight gain and food intake were recorded. The arcuate expression of neuropeptide Y (NPY) and plasma corticosterone levels were analyzed on PND 29 and 40. Results: Decrease in weight gain by repeated fasting/RF cycles was smaller in MS pups than in NH. Interestingly, weight changes responding to fasting or RF increased in MS/RF compared with NH/RF. Compensatory hyperphagia was diminished in NH/RF after the third fasting trial, but persisted in MS/RF throughout the experimental period. The arcuate expression of NPY mRNA responding to food deprivation was blunted, but elevation of plasma corticosterone exaggerated, in the MS group, compared to the NH group, on PND 29 after the first fasting session. However, both the arcuate NPY mRNA and plasma corticosterone levels were increased in MS/RF, but not in NH/RF, on PND 40 after the six sets of fasting/RF cycles, compared to the free FC groups. Conclusion: Experience of neonatal MS may lead to an exaggerated feeding response to repeated fasting/RF challenges at adolescence, perhaps, due to increased responsiveness of the hypothalamic-pituitary-adrenal gland axis. Additionally, the results suggested that an increased action of the hypothalamic NPY may not be necessary to induce compensatory hyperphagia following food deprivation.

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Depressive behaviors and decreased expression of serotonin reuptake transporter in rats that experienced neonatal maternal separation

Cited by 201 publications

References 46 publications

The arcuate NPY, POMC, and CART expressions responding to food deprivation are exaggerated in young female rats that experienced neonatal maternal separation

The arcuate NPY, POMC, and CART expressions responding to food deprivation are exaggerated in young female rats that experienced neonatal maternal separation

Enduring good memories of infant trauma: Rescue of adult neurobehavioral deficits via amygdala serotonin and corticosterone interaction

Sustained hyperphagia in adolescent rats that experienced neonatal maternal separation

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