Cocaine self-administration reinforced on a progressive ratio schedule decreases with continuous D-amphetamine treatment in rats

Psychopharmacology (Berl). 2008 Nov;200(4):465-73. doi: 10.1007/s00213-008-1222-8. Epub 2008 Jul 6.


Rationale: To date, there is no medication specifically approved for cocaine addiction. Agonist medications are used clinically in the treatment of other addictions, which suggests that this method of drug therapy could potentially be successful in treating cocaine addiction as well.

Objective: The objective of this study was to determine the effect of extended D-amphetamine treatment on responding on a progressive ratio (PR) schedule reinforced by cocaine.

Materials and methods: Rats were trained to self-administer cocaine (0.19, 0.38, 0.75, or 1.5 mg/kg/injection) or food on a PR schedule. After stable baseline breakpoints (the number of reinforcers earned in one session) were established over 3 days, animals were implanted with osmotic mini-pumps that continuously delivered D-amphetamine (5 mg/kg/day) for a duration of either 7 or 14 days. Breakpoints were then determined during and/or after this treatment period.

Results: Rats demonstrated dose-dependent decreases in cocaine-reinforced responding over the D-amphetamine treatment period. Breakpoints for doses of 0.75 mg/kg/injection and below decreased significantly when compared to baseline and remained decreased for up to 14 days after mini-pump removal, whereas those for the highest dose of cocaine remained unchanged. Additionally, D-amphetamine treatment during a 14-day abstinence period from cocaine self-administration had no effect on breakpoints when tested the day after mini-pump removal.

Conclusions: These data suggest that the reduction in cocaine-reinforced responding after continuous D-amphetamine treatment cannot be accounted for by tolerance alone. Instead, the roles of learning and the interaction between cocaine and D-amphetamine must be considered and examined in future studies.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Central Nervous System Stimulants / pharmacology*
  • Cocaine / administration & dosage*
  • Cocaine-Related Disorders / drug therapy*
  • Dextroamphetamine / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Reinforcement Schedule
  • Self Administration


  • Central Nervous System Stimulants
  • Cocaine
  • Dextroamphetamine