title: Long-term consequences of neonatal rearing on central corticotropin-releasing factor systems in adult male rat offspring.
abstract: In a series of studies on the long-term consequences of neonatal rearing, we compared hypothalamic and extrahypothalamic central corticotropin-releasing factor (CRF) systems in male rats reared under conditions of animal facility rearing, nonhandling (HMS0), handling with brief maternal separation for 15 min (HMS15), or handling with moderate maternal separation for 180 min (HMS180) daily from postnatal days 2-14. CRF-like immunoreactivity (CRFir) was elevated in lumbar cerebrospinal fluid of adult HMS180 and HMS0 rats relative to the other groups. In the paraventricular nucleus, central nucleus of the amygdala, bed nucleus of the stria terminalis, and locus coeruleus, CRFir and CRF mRNA levels were significantly elevated in HMS0 and HMS180 rats. Neonatal maternal separation was associated with regionally specific alterations in CRF receptor type 1 (CRF1) mRNA density in HMS180 rats. No rearing-associated differences in CRF2alpha binding were apparent in either the lateral septum or the ventromedial hypothalamus. These findings indicate that early rearing conditions can permanently alter the developmental set-point of central CRF systems, and potentially influence the expression of behavioral and endocrine responses to stress throughout life, thereby providing a possible neurobiological substrate for the relationship between early life events and increased vulnerability for hypothalamic-pituitary-adrenal axis and coping skill alterations and the frequency of mood disorders in patients with a history of such experiences.
authors.affiliation: Stress Neurobiology Laboratory, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 1639 Pierce Drive, Atlanta, GA 30322, USA. pplotzky@emory.edu
authors.forename: Paul M
authors.initials: PM
authors.lastname: Plotsky
authors.forename: K V
authors.initials: KV
authors.lastname: Thrivikraman
authors.forename: Charles B
authors.initials: CB
authors.lastname: Nemeroff
authors.forename: Christian
authors.initials: C
authors.lastname: Caldji
authors.forename: Shakti
authors.initials: S
authors.lastname: Sharma
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Meaney
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000134:cerebrospinal fluid / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001522:Behavior, Animal / Q000502:physiology; D003345:Corticosterone / Q000134:cerebrospinal fluid / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism / Q000502:physiology*; D005260:Female; D007031:Hypothalamus / Q000502:physiology; D007091:Image Processing, Computer-Assisted; D017403:In Situ Hybridization; D008297:Male; D010812:Physical Stimulation; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011863:Radioimmunoassay; D051381:Rats; D020318:Rats, Long-Evans; D018019:Receptors, Corticotropin-Releasing Hormone / Q000096:biosynthesis / Q000235:genetics; D013216:Reflex, Startle; D013315:Stress, Psychological / Q000503:physiopathology
chemical_list: D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone