Enhanced reactivity and vulnerability to cocaine following methylphenidate treatment in adolescent rats

Neuropsychopharmacology. 2001 Nov;25(5):651-61. doi: 10.1016/S0893-133X(01)00281-0.


Treatment of attention deficit hyperactivity disorder with the psychostimulant drug methylphenidate (MP) has increased dramatically among schoolchildren. We tested whether repeated exposure to moderate doses of MP (5 and 10 mg/kg IP for 5 or 7 days) in adolescent rats increased reactivity to cocaine measured by motor responses (ambulations and rearing) to a cocaine challenge in adulthood. We later tested whether repeated exposure to a low dose of MP (2 mg/kg IP for 7 days) enhanced the psychomotor effects of cocaine, measured by different challenge doses (0-30 mg/kg) as well as to the reinforcing effects of cocaine, measured by self-administration of low-dose infusion (75 microg/kg, IV). We found that exposure to moderate doses of MP enhanced psychomotor responses to cocaine but exposure to a low dose only increased cocaine self-administration. These results suggest that adolescent exposure to low doses of MP in rats may increase the incentive value of low reinforcers, thereby rendering adult rats more susceptible to cocaine self-administration.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects*
  • Central Nervous System Stimulants / pharmacology
  • Cocaine / pharmacokinetics
  • Cocaine / pharmacology*
  • Dopamine Uptake Inhibitors / pharmacokinetics
  • Dopamine Uptake Inhibitors / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Male
  • Methylphenidate / pharmacology*
  • Motor Activity / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Self Administration


  • Central Nervous System Stimulants
  • Dopamine Uptake Inhibitors
  • Methylphenidate
  • Cocaine