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Methylphenidate administration reverts attentional inflexibility in adolescent rats submitted to a model of neonatal

Patrícia Maidana Miguel1, Bruna Ferrary Deniz1, Heloísa Deola Confortim1

  • 1Programa de Pós-Graduação em Neurociências, Instituto de Ciências Básicas da Saúde (ICBS), Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil; Departamento de Ciências Morfológicas, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.

Experimental Neurology
|February 17, 2019
PubMed

Insights

Neonatal hypoxia-ischemia in rats models Attention-Deficit/Hyperactivity Disorder (ADHD) behaviors. Methylphenidate (MPH) improved attentional flexibility and locomotor activity in HI rats, suggesting predictive validity for ADHD treatment studies.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Developmental Psychology

Background:

  • Perinatal complications like birth asphyxia are linked to increased Attention-Deficit/Hyperactivity Disorder (ADHD) risk.
  • Neonatal hypoxia-ischemia (HI) rat models exhibit ADHD-like symptoms, including inattention and impulsivity, with prefrontal cortex dopamine disturbances.
  • The predictive validity of HI models for ADHD pharmacological treatments requires investigation.

Purpose of the Study:

  • To assess methylphenidate (MPH) effects on behavior and dopamine-related proteins in a rat model of neonatal hypoxia-ischemia (HI).
  • To evaluate MPH's impact on exploratory and attentional flexibility behaviors in HI rats.
  • To determine if MPH treatment demonstrates predictive validity for ADHD therapy in this model.

Main Methods:

  • Male Wistar rats underwent neonatal HI at postnatal day 7 or served as controls.
  • Groups received either saline or MPH (2.5 mg/kg) before behavioral testing (postnatal days 30-40) and euthanasia.
  • Behavioral tests included open field and attentional-set shifting task; prefrontal cortex protein analysis (DA D2 receptors, DAT, pTH) was performed via Western blot.

Main Results:

  • MPH increased locomotor activity in HI rats compared to saline-treated HI rats.
  • MPH administration reversed HI-induced attentional inflexibility but impaired attentional set-shifting acquisition in control rats.
  • Neonatal HI led to altered dopamine system proteins in the PFC (decreased D2 receptors and DAT, increased pTH), with enhanced compensatory changes in MPH-treated HI rats.

Conclusions:

  • Methylphenidate (MPH) shows potential in ameliorating specific behavioral deficits and normalizing dopamine-related protein alterations in a neonatal hypoxia-ischemia (HI) rat model.
  • The observed improvements in attentional flexibility and locomotor activity in MPH-treated HI rats support the predictive validity of this model for ADHD treatment research.
  • Findings suggest that MPH's therapeutic effects in ADHD may involve modulating dopamine transmission and compensatory mechanisms in response to early-life insults.

Keywords:
Attention-deficit/hyperactivity disorderAttentional set-shiftingD1D2Dopamine transporter (DAT)Locomotor activityOpen fieldTyrosine hydroxylase (TH)

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