title: Early-life stress increases the survival of midbrain neurons during postnatal development and enhances reward-related and anxiolytic-like behaviors in a sex-dependent fashion.
abstract: Clinical studies have suggested that early-life stress (ELS) increases the risk of psychopathologies that are strongly associated with dysfunction of dopaminergic neurotransmission. Thus, ELS may interfere with the development and maturation of the dopaminergic system; however, the mechanisms involved in such interference are poorly understood. In the present study, we investigated the effect of ELS on the survival of specific populations of neurons in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) during postnatal development. First, we injected bromodeoxyuridine (BrdU) into pregnant rat dams on embryonic days 12, 13 and 14 to permanently label midbrain neurons. Then, after birth, the dams and litters were subjected to a maternal separation (MS) procedure to model ELS conditions. The number of BrdU+ neurons and the total number of neurons (cresyl violet+, CV+) were estimated in both male and female juvenile, adolescent, and adult rats. Moreover, sucrose preference and anxiety-like behaviors were studied during adulthood. We found that MS permanently increased the number of BrdU+ and CV+ neurons in the VTA of males. In the SNc, a temporary increase in the number of BrdU+ neurons was observed in juvenile MS males; however, only adult MS males displayed an increase in the number of CV+ neurons. Immunofluorescence analysis implied that MS affected the fate of non-dopaminergic neurons. MS males displayed anxiolytic-like behavior and an increase in sucrose preference. These results suggest that ELS induces distinct dysregulation in the midbrain circuitry of males, which may lead to sex-specific psychopathology of the reward system.
authors.affiliation: Laboratory of Pharmacology and Brain Biostructure, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, 31-343 Kraków, Poland. Electronic address: chocyk@if-pan.krakow.pl.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Chocyk
authors.affiliation: Laboratory of Pharmacology and Brain Biostructure, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, 31-343 Kraków, Poland.
authors.forename: Iwona
authors.initials: I
authors.lastname: Majcher-Maślanka
authors.affiliation: Laboratory of Pharmacology and Brain Biostructure, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, 31-343 Kraków, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Przyborowska
authors.affiliation: Laboratory of Pharmacology and Brain Biostructure, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, 31-343 Kraków, Poland.
authors.forename: Marzena
authors.initials: M
authors.lastname: Maćkowiak
authors.affiliation: Laboratory of Pharmacology and Brain Biostructure, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, 31-343 Kraków, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Wędzony
mesh_terms: D000221:Adaptation, Ocular; D000367:Age Factors; D000818:Animals; D001010:Anxiety, Separation / Q000209:etiology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count; D005260:Female; D005518:Food Preferences; D008297:Male; D008426:Maternal Deprivation; D008636:Mesencephalon / Q000254:growth & development / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000473:pathology*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D012201:Reward; D012727:Sex Characteristics; D013315:Stress, Psychological / Q000150:complications / Q000473:pathology / Q000523:psychology; D013395:Sucrose / Q000008:administration & dosage; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D009419:Nerve Tissue Proteins; D013395:Sucrose; D014446:Tyrosine 3-Monooxygenase; D001973:Bromodeoxyuridine
keywords: Anxiety; Early-life stress; Substantia nigra; Sucrose preference; Ventral tegmental area