Systematic review and meta-analysis of the behavioral effects of methylphenidate in the spontaneously hypertensive rat model of attention-deficit/hyperactivity disorder

Neurosci Biobehav Rev. 2019 May:100:166-179. doi: 10.1016/j.neubiorev.2019.02.019. Epub 2019 Feb 28.

Abstract

The spontaneously hypertensive rats (SHR) are the most widely used model for ADHD. While face and construct validity are consolidated, questions remain about the predictive validity of the SHR model. We aim at summarizing the evidence for the predictive validity of SHR by evaluating its ability to respond to methylphenidate (MPH), the most well documented treatment for ADHD. A systematic review was carried out to identify studies evaluating MPH effects on SHR behavior. Studies (n=36) were grouped into locomotion, attention, impulsivity or memory, and a meta-analysis was performed. Meta-regression, sensitivity, heterogeneity, and publication bias analyses were also conducted. MPH increased attentional and mnemonic performances in the SHR model and decreased impulsivity in a dose-dependent manner. However, MPH did not reduce hyperactivity in low and medium doses, while increased locomotor activity in high doses. Thus, since the paradoxical effect of stimulant in reducing hyperactivity was not observed in the SHR model, our study does not fully support the predictive validity of SHR, questioning their validity as an animal model for ADHD.

Keywords: ADHD; Animal model; Meta-analysis; Methylphenidate; Predictive validity; SHR; Systematic review.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Animals
  • Attention / drug effects
  • Attention Deficit Disorder with Hyperactivity / psychology*
  • Behavior, Animal / drug effects*
  • Central Nervous System Stimulants / administration & dosage*
  • Disease Models, Animal*
  • Dose-Response Relationship, Drug
  • Impulsive Behavior / drug effects
  • Memory / drug effects
  • Methylphenidate / administration & dosage*
  • Rats, Inbred SHR
  • Reproducibility of Results

Substances

  • Central Nervous System Stimulants
  • Methylphenidate