Individual differences in novelty-seeking behavior in spontaneously hypertensive rats: Enhanced sensitivity to the reinforcing effect of methylphenidate in the high novelty-preferring subpopulation

J Neurosci Methods. 2015 Aug 30:252:48-54. doi: 10.1016/j.jneumeth.2014.08.019. Epub 2014 Aug 26.

Abstract

Background: High novelty seeking has been assumed to predict vulnerability to use addictive drugs. Notably, it is also a symptom associated with attention-deficit/hyperactivity disorder (ADHD). The aim of this study was to identify whether spontaneously hypertensive rats (SHRs), putative animal models of ADHD, display individual differences in novelty-seeking behavior, and whether high novelty-seeking SHRs show enhanced sensitivity to the reinforcing effect of methylphenidate, the most commonly prescribed stimulant ADHD medication.

Methods: First, we established that SHRs show higher levels of novelty-seeking behavior than their normotensive control strain, Wistar Kyoto (WKY) rats. Novelty seeking was measured in two tests: open field test in a novel test arena, and novel object preference tests. Thereafter, SHRs were classified into high responders (HR) or low responders (LR), high novelty-preferring (HNP) or low novelty-preferring (LNP) rats, based on individual scores in the two behavioral assays. Methylphenidate self-administration was assessed thereafter.

Results: SHRs showed higher levels of novelty-seeking behavior than WKY rats. HR/LR and HNP/LNP subgroups were identified. HR and LR rats showed comparable rates of methylphenidate self-administration. However, HNP SHRs worked more for methylphenidate infusions than their LNP counterparts.

Conclusions: We showed some evidence on inter-individual variations in novelty seeking in SHRs. Importantly, we demonstrated enhanced sensitivity of HNP SHRs to the reinforcing effect of methylphenidate, indicating a "drug-vulnerable" SHR subpopulation. These findings are important as they may provide basis for a potential screening tool to identify a subset of ADHD patients (i.e. high novelty seekers) who may be at risk for misusing/abusing methylphenidate.

Keywords: ADHD; Addiction; Methylphenidate; Novelty-seeking; SHR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Attention Deficit Disorder with Hyperactivity / physiopathology*
  • Central Nervous System Stimulants / administration & dosage*
  • Conditioning, Operant / drug effects
  • Disease Models, Animal
  • Exploratory Behavior / drug effects*
  • Individuality*
  • Male
  • Methylphenidate / administration & dosage*
  • Motor Activity / drug effects
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Reinforcement, Psychology*
  • Self Administration

Substances

  • Central Nervous System Stimulants
  • Methylphenidate