Cocaine tolerance: acute versus chronic effects as dependent upon fixed-ratio size.
Tolerance to cocaine’s behavior-slowing effect disappears on easy work but sticks around when the schedule is hard.
01Research in Context
What this study did
Scientists gave pigeons cocaine before they pecked a key for food.
The birds worked under three fixed-ratio schedules: small, medium, and large.
They first tested one shot of cocaine. Then they gave the drug every day to see if tolerance would grow.
What they found
One hit of cocaine slowed the birds down on every schedule.
After daily doses, the birds pecked normally again on the small and medium ratios.
On the largest ratio, the drug still slowed them down—tolerance did not form.
How this fits with other research
Hus et al. (2013) later showed tolerance can grow even when the daily dose never changes behavior. That seems opposite, but they used a dose too small to hurt responding at the start. H et al. used a dose that always disrupted, so only easy ratios recovered.
Cryan et al. (1996) kept the large ratio and instead changed how hungry the birds were. Hungry birds developed tolerance faster on that same large ratio, showing that motivation, not just ratio size, shapes tolerance.
Lerner et al. (2012) switched the task to memory matching and still saw tolerance, proving the effect is not tied to key-peck rate alone.
Why it matters
If you run drug-behavior studies, schedule difficulty can hide or show tolerance. A tough schedule may keep the drug effect alive, making you think tolerance failed. Ease the response requirement and tolerance may appear. Test at least two workload levels before you decide a drug effect is permanent.
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Plot response rate across two FR sizes after any drug probe—if tolerance only shows on the smaller one, your schedule, not the dose, is the key.
02At a glance
03Original abstract
The effects of cocaine on operant behavior were studied by examining fixed-ratio value as a factor in the development of tolerance. Pigeons pecked a response key under a three-component multiple schedule, with each bird being exposed to fixed-ratio values that were categorized as small, medium, or large. Administered acutely, cocaine (1.0 to 10.0 mg/kg) produced dose-related decreases in overall rate of responding. Responding maintained by the largest ratio was decreased by lower doses than those required to reduce rates of responding maintained by the other two ratio schedules. Following repeated daily administration of 5.6 mg/kg of cocaine, dose-effect functions (obtained from sessions during the chronic regimen by making substitutions for the daily dose) indicated tolerance under the smaller ratios, but no tolerance or less tolerance under the largest ratio. Thus, whether tolerance developed, and the degree to which it developed, depended on the ratio value. The results are partially consistent with the notion that tolerance to drug effects on schedule-controlled behavior will develop if drug administration initially reduces reinforcement frequency, but they indicate that reinforcement loss alone is not a sufficient condition for the generation of tolerance under such conditions. The findings suggest that amount of responding required for reinforcement, or "effort," may contribute to the development of tolerance to effects of cocaine.
Journal of the experimental analysis of behavior, 1987 · doi:10.1901/jeab.1987.47-363