title: Early-life stress disrupts attachment learning: the role of amygdala corticosterone, locus ceruleus corticotropin releasing hormone, and olfactory bulb norepinephrine.
abstract: Infant rats require maternal odor learning to guide pups' proximity-seeking of the mother and nursing. Maternal odor learning occurs using a simple learning circuit including robust olfactory bulb norepinephrine (NE), release from the locus ceruleus (LC), and amygdala suppression by low corticosterone (CORT). Early-life stress increases NE but also CORT, and we questioned whether early-life stress disrupted attachment learning and its neural correlates [2-deoxyglucose (2-DG) autoradiography]. Neonatal rats were normally reared or stressed-reared during the first 6 d of life by providing the mother with insufficient bedding for nest building and were odor-0.5 mA shock conditioned at 7 d old. Normally reared paired pups exhibited typical odor approach learning and associated olfactory bulb enhanced 2-DG uptake. However, stressed-reared pups showed odor avoidance learning and both olfactory bulb and amygdala 2-DG uptake enhancement. Furthermore, stressed-reared pups had elevated CORT levels, and systemic CORT antagonist injection reestablished the age-appropriate odor-preference learning, enhanced olfactory bulb, and attenuated amygdala 2-DG. We also assessed the neural mechanism for stressed-reared pups' abnormal behavior in a more controlled environment by injecting normally reared pups with CORT. This was sufficient to produce odor aversion, as well as dual amygdala and olfactory bulb enhanced 2-DG uptake. Moreover, we assessed a unique cascade of neural events for the aberrant effects of stress rearing: the amygdala-LC-olfactory bulb pathway. Intra-amygdala CORT or intra-LC corticotropin releasing hormone (CRH) infusion supported aversion learning with intra-LC CRH infusion associated with increased olfactory bulb NE (microdialysis). These results suggest that early-life stress disturbs attachment behavior via a unique cascade of events (amygdala-LC-olfactory bulb).
authors.affiliation: Emotional Brain Institute, Nathan Kline Institute, Orangeburg, New York 10962, USA. SMoriceau@nki.rfmh.org
authors.forename: Stephanie
authors.initials: S
authors.lastname: Moriceau
authors.forename: Kiseko
authors.initials: K
authors.lastname: Shionoya
authors.forename: Katherine
authors.initials: K
authors.lastname: Jakubs
authors.forename: Regina M
authors.initials: RM
authors.lastname: Sullivan
mesh_terms: D000367:Age Factors; D000679:Amygdala / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001245:Association Learning / Q000502:physiology; D003345:Corticosterone / Q000502:physiology*; D003346:Corticotropin-Releasing Hormone / Q000502:physiology*; D005260:Female; D008125:Locus Coeruleus / Q000502:physiology*; D008297:Male; D008425:Maternal Behavior / Q000502:physiology / Q000523:psychology; D009638:Norepinephrine / Q000502:physiology*; D009830:Olfactory Bulb / Q000502:physiology*; D051381:Rats; D020318:Rats, Long-Evans; D013315:Stress, Psychological / Q000378:metabolism* / Q000523:psychology
chemical_list: D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone; D009638:Norepinephrine