Methylphenidate amplifies the potency and reinforcing effects of amphetamines by increasing dopamine transporter expression

Nat Commun. 2013;4:2720. doi: 10.1038/ncomms3720.

Abstract

Methylphenidate (MPH) is commonly diverted for recreational use, but the neurobiological consequences of exposure to MPH at high, abused doses are not well defined. Here we show that MPH self-administration in rats increases dopamine transporter (DAT) levels and enhances the potency of MPH and amphetamine on dopamine responses and drug-seeking behaviours, without altering cocaine effects. Genetic overexpression of the DAT in mice mimics these effects, confirming that MPH self-administration-induced increases in DAT levels are sufficient to induce the changes. Further, this work outlines a basic mechanism by which increases in DAT levels, regardless of how they occur, are capable of increasing the rewarding and reinforcing effects of select psychostimulant drugs, and suggests that individuals with elevated DAT levels, such as ADHD sufferers, may be more susceptible to the addictive effects of amphetamine-like drugs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Amphetamines / pharmacology*
  • Animals
  • Behavior, Animal
  • Brain / drug effects
  • Brain / pathology
  • Central Nervous System Stimulants / pharmacology
  • Cocaine / pharmacology
  • Dopamine Plasma Membrane Transport Proteins / metabolism*
  • Gene Expression Regulation*
  • Locomotion
  • Male
  • Methylphenidate / pharmacology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Rats
  • Rats, Sprague-Dawley
  • Reinforcement, Psychology
  • Self Administration

Substances

  • Amphetamines
  • Central Nervous System Stimulants
  • Dopamine Plasma Membrane Transport Proteins
  • Methylphenidate
  • Cocaine