title: Prefrontal cortex dysfunction in hypoxic-ischaemic encephalopathy contributes to executive function impairments in rats: Potential contribution for attention-deficit/hyperactivity disorder.
abstract: The attention-deficit/hyperactivity disorder (ADHD) compromises the quality of life of individuals including adaptation to the social environment. ADHD aetiology includes perinatal conditions such as hypoxic-ischaemic events; preclinical studies have demonstrated attentional deficits and impulsive-hyperactive outcomes after neonatal hypoxic and/or ischaemic intervention, but data are missing to understand this relationship. Thus, the aim of this study was to evaluate executive function (EF) and impulsivity, and tissue integrity and dopaminergic function in the prefrontal cortex (PFC) of rats submitted to hypoxia-ischaemia (HI).
  
  
  
  At postnatal day (PND) 7, male Wistar rats were divided into control (n = 10) and HI groups (n = 11) and the HI procedure was conducted. At PND60, the animals were tested in the attentional set-shifting (ASS) task to EF and in the tolerance to delay of reward for assessment of impulsivity. After, morphological analysis and the dopaminergic system were evaluated in the PFC.
  
  
  
  Animals subjected to HI had impairments in EF evidenced by a behavioural inflexibility that was correlated to PFC atrophy. Moreover, HI animals presented reduced D2 receptors in the ipsilateral side of ischaemia in the PFC.
  
  
  
  Animals submitted to HI presented impaired EF associated with tissue atrophy and dopaminergic disturbance in the PFC.
authors.affiliation: a Programa de Pós-Graduação em Neurociências, Instituto de Ciências Básicas da Saúde (ICBS) , Universidade Federal do Rio Grande do Sul , Porto Alegre , RS , Brazil.|b Departamento de Ciências Morfológicas, ICBS , Universidade Federal do Rio Grande do Sul , Porto Alegre , RS , Brazil.
authors.forename: Patrícia Maidana
authors.initials: PM
authors.lastname: Miguel
authors.affiliation: a Programa de Pós-Graduação em Neurociências, Instituto de Ciências Básicas da Saúde (ICBS) , Universidade Federal do Rio Grande do Sul , Porto Alegre , RS , Brazil.|b Departamento de Ciências Morfológicas, ICBS , Universidade Federal do Rio Grande do Sul , Porto Alegre , RS , Brazil.
authors.forename: Bruna Ferrary
authors.initials: BF
authors.lastname: Deniz
authors.affiliation: b Departamento de Ciências Morfológicas, ICBS , Universidade Federal do Rio Grande do Sul , Porto Alegre , RS , Brazil.
authors.forename: Iohanna
authors.initials: I
authors.lastname: Deckmann
authors.affiliation: a Programa de Pós-Graduação em Neurociências, Instituto de Ciências Básicas da Saúde (ICBS) , Universidade Federal do Rio Grande do Sul , Porto Alegre , RS , Brazil.|b Departamento de Ciências Morfológicas, ICBS , Universidade Federal do Rio Grande do Sul , Porto Alegre , RS , Brazil.
authors.forename: Heloísa Deola
authors.initials: HD
authors.lastname: Confortim
authors.affiliation: a Programa de Pós-Graduação em Neurociências, Instituto de Ciências Básicas da Saúde (ICBS) , Universidade Federal do Rio Grande do Sul , Porto Alegre , RS , Brazil.|b Departamento de Ciências Morfológicas, ICBS , Universidade Federal do Rio Grande do Sul , Porto Alegre , RS , Brazil.
authors.forename: Ramiro
authors.initials: R
authors.lastname: Diaz
authors.affiliation: a Programa de Pós-Graduação em Neurociências, Instituto de Ciências Básicas da Saúde (ICBS) , Universidade Federal do Rio Grande do Sul , Porto Alegre , RS , Brazil.
authors.forename: Daniela Pereira
authors.initials: DP
authors.lastname: Laureano
authors.affiliation: a Programa de Pós-Graduação em Neurociências, Instituto de Ciências Básicas da Saúde (ICBS) , Universidade Federal do Rio Grande do Sul , Porto Alegre , RS , Brazil.|c Programa de Pós-Graduação em Saúde da Criança e do Adolescente, Faculdade de Medicina , Universidade Federal do Rio Grande do Sul , Porto Alegre , RS , Brazil.|d Ludmer Centre for Neuroinformatics and Mental Health , Douglas Mental Health University Institute, McGill University , Montreal , QC , Canada.
authors.forename: Patrícia Pelufo
authors.initials: PP
authors.lastname: Silveira
authors.affiliation: a Programa de Pós-Graduação em Neurociências, Instituto de Ciências Básicas da Saúde (ICBS) , Universidade Federal do Rio Grande do Sul , Porto Alegre , RS , Brazil.|b Departamento de Ciências Morfológicas, ICBS , Universidade Federal do Rio Grande do Sul , Porto Alegre , RS , Brazil.
authors.forename: Lenir Orlandi
authors.initials: LO
authors.lastname: Pereira
mesh_terms: D000818:Animals; D001284:Atrophy; D001288:Attention; D001289:Attention Deficit Disorder with Hyperactivity / Q000503:physiopathology*; D001522:Behavior, Animal; D004298:Dopamine / Q000378:metabolism; D056344:Executive Function; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism / Q000503:physiopathology*; D007175:Impulsive Behavior; D008297:Male; D017397:Prefrontal Cortex / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D012201:Reward
chemical_list: D004298:Dopamine
keywords: ADHD; Attentional set shifting; D2 receptor; behavioural flexibility; tolerance to delay of reward