Drug effects on repeated acquisition: comparison of cumulative and non-cumulative dosing.
Cumulative dosing saves time but can make drug effects look bigger or smaller depending on the drug.
01Research in Context
What this study did
The team gave three drugs to lab animals using two dosing styles. One style added each dose on top of the last. The other gave each dose on separate days.
They watched how the animals learned a new chain of button presses after every drug shot.
What they found
Phencyclidine and pentobarbital looked stronger when each dose was given alone. D-amphetamine looked stronger when doses were piled up.
Cumulative dosing changed the size of the drug effect, not just the speed of the test.
How this fits with other research
Webb et al. (1999) ran a similar comparison in humans with triazolam. They also saw curve shifts, yet still liked the time-saving one-day method. The animal and human data line up: cumulative dosing works, but the numbers move.
Wilkie et al. (1981) used the same repeated-acquisition task to show naloxone blocks morphine errors. That paper proves the task is sensitive to drug interactions, so the dosing-style differences seen here are likely real.
McMillan (1979) and Hearst (1960) both found that d-amphetamine cuts response rate under fixed schedules. The current study shows the same drug also hurts new learning, and the size of that hurt depends on how you give the doses.
Why it matters
If you ever compare drug effects across studies, check how the doses were given. A "strong" result might look weak simply because the earlier doses were still in the body. When you read pre-clinical charts, note whether the curve came from one long session or many short ones.
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02At a glance
03Original abstract
Pigeons acquired a different four-response chain each session by responding sequentially on three keys in the presence of a sequence of four colors. The response chain was maintained by food presentation under a fixed-ratio schedule. Errors produced a brief timeout but did not reset the chain. Each day there were four 15-minute sessions, with a 10-minute inter-session interval. Cumulative dose-effect curves for phencyclidine, pentobarbital, and d-amphetamine were obtained by giving an injection before each of the four sessions; successive injections increased the cumulative dose in equally spaced logarithmic steps. For comparison, non-cumulative doses of each drug (i.e., doses not preceded by other doses on the same day) were also tested. As the cumulative dose of each drug increased, the overall response rate decreased, the percent errors increased, and there was less within-session error reduction (acquisition). With phencyclidine and pentobarbital, the rate-decreasing and error-increasing effects tended to be greater with a non-cumulative dose than with the corresponding cumulative dose. In contrast, with d-amphetamine, the effects were considerably greater with the cumulative doses. The results indicate that although the cumulative-dosing procedure saved a substantial amount of time in determining dose-effect curves, there were quantitative differences in effects between cumulative and non-cumulative doses.
Journal of the experimental analysis of behavior, 1983 · doi:10.1901/jeab.1983.39-175