Dose-dependent effects but not sensitization of DRL 45-s performance by oral d-amphetamine with cumulative- and repeated-dosing regimens

Behav Pharmacol. 1999 Dec;10(8):739-46. doi: 10.1097/00008877-199912000-00005.


The effects of d-amphetamine (AMPH) on a food-reinforced DRL 45-s schedule were evaluated using both cumulative- and repeated-dosing drug regimens. These two dosing regimens were designed to evaluate sensitization as a shift in the dose-response relationship, inasmuch as a range of doses was imposed within each dosing session. Daily 190-min sessions were composed of five 35-min subsessions separated by 3-min time-out periods. For selected sessions, five cumulative or repeated oral doses of AMPH were administered across the session, with a dose given during each of the time-out periods prior to the start of each subsession. Drug sessions were separated by intervals of 7-l0 days of non-drug sessions. Four cumulative dose-effect functions for AMPH were determined: for each dose-effect determination session, increasing doses (0.5, 1, 2, 4, 8 mg/kg gavage) were successively administered prior to each subsession. Four dose-effect functions were then determined in which a 0.5 mg/kg AMPH dose was repeated for each subsession (repetitive-dose regimen) rather than escalating subsession dose size. Then, four additional functions were determined using a larger repetitive dose of 1 mg/kg AMPH. Cumulative doses resulted in a leftward shift in the inter-response times (IRT) distribution accompanied by dose-dependent increases in subcriterion responses (< 45 s) and decreases in reinforced responses. The repeated doses of 0.5 or 1 mg/kg AMPH also resulted in progressive intrasession increases in subcriterion responses and decreases in reinforced responses. Although intrasession, accumulating dose effects were evident and statistically significant, there was no statistical significance or trend supporting sensitization of differential reinforcement of low-rate (DRL) responding with either cumulative- or repeated-dosing regimens across drugging sessions, unlike a previous, similar study in which oral cocaine resulted in robust sensitization.

Publication types

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

MeSH terms

  • Administration, Oral
  • Animals
  • Central Nervous System Stimulants / administration & dosage*
  • Central Nervous System Stimulants / pharmacology*
  • Conditioning, Operant / drug effects*
  • Dextroamphetamine / administration & dosage*
  • Dextroamphetamine / pharmacology*
  • Dose-Response Relationship, Drug
  • Food
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Reinforcement Schedule*


  • Central Nervous System Stimulants
  • Dextroamphetamine