title: Effects of early and late neonatal bromocriptine treatment on hypothalamic neuropeptides, dopaminergic reward system and behavior of adult rats.
abstract: In humans, bromocriptine (BRO) is used as a treatment for many disorders, such as prolactinomas, even during pregnancy and lactation. Previously we demonstrated that maternal BRO treatment at the end of lactation programs offspring for obesity and several endocrine dysfunctions. Here, we studied the long-term effects of direct BRO injection in neonatal Wistar rats on their dopaminergic pathway, anxiety-like behavior and locomotor activity at adulthood. Male pups were either s.c. injected with BRO (0.1μg/once daily) from postnatal day (PN) 1 to 10 or from PN11 to 20. Controls were injected with methanol-saline. Body mass, food intake, neuropeptides, dopamine pathway parameters, anxiety-like behavior and locomotor activity were analyzed. The dopamine pathway was analyzed in the ventral tegmental area (VTA), nucleus accumbens (NAc) and dorsal striatum (DS) at PN180. PN1-10 BRO-treated animals had normal body mass and adiposity but lower food intake and plasma prolactin (PRL). This group had higher POMC in the arcuate nucleus (ARC), higher tyrosine hydroxylase (TH) in the VTA, higher dopa decarboxylase (DDc), higher D2R and μu-opioid receptor in the NAc. Concerning behavior in elevated plus maze (EPM), BRO-treated animals displayed more anxiety-like behaviors. PN11-20 BRO-treated showed normal body mass and adiposity but higher food intake and plasma PRL. This group had lower POMC in the ARC, lower TH in the VTA and lower DAT in the NAc. BRO-treated animals showed less anxiety-like behaviors in the EPM. Thus, neonatal BRO injection, depending on the time of treatment, leads to different long-term dysfunctions in the dopaminergic reward system, food intake behavior and anxiety levels, findings that could be partially due to PRL and POMC changes.
authors.affiliation: Laboratory of Endocrine Physiology, Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, RJ 20551-030, Brazil.
authors.forename: Janaine C
authors.initials: JC
authors.lastname: Carvalho
authors.affiliation: Laboratory of Endocrine Physiology, Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, RJ 20551-030, Brazil. Electronic address: pclisboa@uerj.br.
authors.forename: Patricia C
authors.initials: PC
authors.lastname: Lisboa
authors.affiliation: Laboratory of Endocrine Physiology, Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, RJ 20551-030, Brazil.
authors.forename: Elaine
authors.initials: E
authors.lastname: de Oliveira
authors.affiliation: Laboratory of Endocrine Physiology, Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, RJ 20551-030, Brazil.
authors.forename: Nayara
authors.initials: N
authors.lastname: Peixoto-Silva
authors.affiliation: Laboratory of Endocrine Physiology, Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, RJ 20551-030, Brazil.
authors.forename: Cintia R
authors.initials: CR
authors.lastname: Pinheiro
authors.affiliation: Laboratory of Endocrine Physiology, Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, RJ 20551-030, Brazil; Laboratory of Neurophysiology, Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, RJ 20551-030, Brazil.
authors.forename: Mabel C
authors.initials: MC
authors.lastname: Fraga
authors.affiliation: Laboratory of Neurophysiology, Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, RJ 20551-030, Brazil.
authors.forename: Sylvio
authors.initials: S
authors.lastname: Claudio-Neto
authors.affiliation: Department of Physiology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP 14049-900, Brazil.
authors.forename: Celso R
authors.initials: CR
authors.lastname: Franci
authors.affiliation: Laboratory of Neurophysiology, Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, RJ 20551-030, Brazil.
authors.forename: Alex C
authors.initials: AC
authors.lastname: Manhães
authors.affiliation: Laboratory of Endocrine Physiology, Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, RJ 20551-030, Brazil.
authors.forename: Egberto G
authors.initials: EG
authors.lastname: Moura
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D001971:Bromocriptine / Q000008:administration & dosage*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000008:administration & dosage*; D008124:Locomotion / Q000187:drug effects; D008297:Male; D009478:Neuropeptide Y / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012201:Reward; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism
chemical_list: D018491:Dopamine Agonists; D009478:Neuropeptide Y; D009479:Neuropeptides; D001971:Bromocriptine; D011333:Pro-Opiomelanocortin; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine
keywords: anxiety; dopamine; lactation; locomotor activity; programing; rat