The progressive ratio and fixed ratio 1 schedules of cocaine self-administration in rats convey the same information

Sci Rep. 2022 Nov 16;12(1):19683. doi: 10.1038/s41598-022-24173-x.


Progressive ratio (PR) schedules of drug delivery are used to determine the 'motivational' state of an animal and drug 'reinforcing efficacy'. This widely held interpretation is supported mainly by the observation that the PR breakpoint (BP) is proportional to the unit dose of self-administered drug. The compulsion zone theory of cocaine self-administration was applied to determine whether it can explain the pattern of lever-pressing behavior and cocaine injections under the PR schedule in rats. This theory states that cocaine induces lever pressing when levels are below the satiety threshold and above the priming/remission threshold. Rats were trained to self-administer cocaine on a fixed ratio FR1 schedule over a range of cocaine unit doses. Then they were switched to a PR schedule. Typical for the self-administration under a PR schedule, long post-injection pauses occurred when calculated cocaine levels were in the satiety zone. The compulsion zone theory interprets BP simply as the maximal number of responses which rats can perform after an injection while cocaine levels remain within the compulsion zone. The thresholds delineating the compulsion zone were very stable and independent of the self-administration schedule. PR and fixed ratio schedules convey the same pharmacokinetic/pharmacodynamic information, i.e., these two schedules are invariant.

MeSH terms

  • Animals
  • Cocaine* / pharmacology
  • Conditioning, Operant
  • Rats
  • Rats, Sprague-Dawley
  • Reinforcement Schedule
  • Self Administration


  • Cocaine