Effects of dopamine antagonists and accumbens dopamine depletions on time-constrained progressive-ratio performance

Pharmacol Biochem Behav. 1998 Dec;61(4):341-8. doi: 10.1016/s0091-3057(98)00112-9.


Four experiments were conducted to determine the effects of dopamine (DA) antagonists and DA depletions on progressive-ratio responding for food reinforcement. On this schedule, ratio requirement increased by one response after each reinforcer was obtained, and rats were tested in 30-min sessions. Response rates and highest ratio completed were reduced in a dose-related manner by systemic injections of the D1 antagonist SCH 23390, and also by the D2 antagonists haloperidol and raclopride. Drug-treated rats also showed reductions in time to complete the last ratio, demonstrating that they had stopped responding before the end of the session. DA depletions produced by injections of 6-OHDA directly into the nucleus accumbens substantially decreased both the number of responses and the highest ratio completed. The deficits in response number and highest ratio completed induced by DA depletions persisted through the first 3 weeks of postsurgical testing, with some recovery by the fourth week. However, the deficits resulting from dopamine depletions were largely a manifestation of a decrease in response rate; although time to complete the last ratio was significantly reduced by dopamine depletions in the first few days of testing, rats recovered on this measure by the fifth day after surgery. Although previous work has shown that performance on several schedules (e.g., continuous, low value ratios, variable interval) is relatively unaffected by accumbens DA depletions, the present data demonstrate that such depletions do produce a substantial and persistent impairment of progressive ratio response output. Rats with accumbens DA depletions appear to have deficits in maintaining the high work output necessary for responding at large ratio values. The relative sparing of responding on some simple schedules, together with the present progressive ratio results, suggest that rats with accumbens DA depletions remain directed toward the acquisition and consumption of food, but they show deficits in work output for food.

Publication types

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

MeSH terms

  • Animals
  • Benzazepines / pharmacology
  • Conditioning, Operant / drug effects*
  • Dopamine / metabolism*
  • Dopamine Antagonists / pharmacology*
  • Dose-Response Relationship, Drug
  • Haloperidol / pharmacology
  • Male
  • Nucleus Accumbens / drug effects*
  • Nucleus Accumbens / metabolism
  • Raclopride
  • Rats
  • Rats, Sprague-Dawley
  • Reinforcement Schedule*
  • Salicylamides / pharmacology
  • Time Factors


  • Benzazepines
  • Dopamine Antagonists
  • Salicylamides
  • Raclopride
  • Haloperidol
  • Dopamine