title: Reduction of the reinforcing effectiveness of cocaine by continuous D-amphetamine treatment in rats: importance of active self-administration during treatment period.
abstract: BACKGROUND
  Continuous administration of D-amphetamine has shown promise as a treatment for psychostimulant addiction. In rodent studies, constant infusion of D-amphetamine (5 mg/kg/day) has been shown to reduce cocaine-reinforced responding in the dose range of 0.19-0.75 mg/kg/inf.
  
  
  OBJECTIVE
  The present study tested whether these effects were a reflection of pharmacological interactions between D-amphetamine and cocaine or if they resulted from associative learning mechanisms
  
  
  METHODS
  After stable progressive ratio (PR) baselines were established, rats were implanted with subcutaneous osmotic minipumps filled with either D-amphetamine (5 mg/kg/day-groups 1 and 2) or saline (group 3). During the treatment period, groups 1 and 3 self-administered cocaine at a dose that was previously shown to produce the most robust effects in combination with D-amphetamine treatment (0.19 mg/kg/inf), while group 2 received passive cocaine infusions.
  
  
  RESULTS
  In replication of previous studies, D-amphetamine treatment resulted in a significant (35 %) decrease in breakpoints relative to saline controls. By contrast, no reductions in breakpoints were observed in animals that received passive cocaine infusions during the treatment period (group 2).
  
  
  CONCLUSIONS
  Active self-administration of cocaine during the treatment period appears to be an important factor in reducing cocaine-reinforced breakpoints. These findings suggest learning mechanisms are involved in the therapeutic effects of continuous D-amphetamine, and pharmacological interaction mechanisms such as cross-tolerance cannot completely account for the observed decreases in cocaine seeking.
authors.affiliation: Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Medical Center BLVD, Winston-Salem, NC, 27157, USA, bzimmer@wakehealth.edu.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Zimmer
authors.forename: Keri A
authors.initials: KA
authors.lastname: Chiodo
authors.forename: David C S
authors.initials: DC
authors.lastname: Roberts
mesh_terms: D000818:Animals; D003042:Cocaine / Q000037:antagonists & inhibitors*; D003913:Dextroamphetamine / Q000494:pharmacology*; D004347:Drug Interactions; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012054:Reinforcement, Psychology; D012646:Self Administration
chemical_list: D003042:Cocaine; D003913:Dextroamphetamine