Estradiol administration to ovariectomized rats potentiates mephedrone-induced disruptions of nonspatial learning.

Scientists gave female rats a simple chain of lever presses to learn. Each rat had to copy a new four-press order every session.

Some rats first got mephedrone, a party drug. Others got mephedrone plus estradiol, the main estrogen. The team counted how fast and how well the animals learned the chain.

Mephedrone alone slowed learning and cut accuracy. Adding estradiol made the damage worse. Higher doses hurt more than lower doses.

The drug-and-hormone combo wrecked both speed and correctness. Even rats that usually learned quickly made many errors.

Gadow et al. (2006) saw the same pattern in pigeons. d-Amphetamine also ruined repeated key-peck chains. The two studies line up: stimulants break reinforced sequence skills.

Locurto et al. (1980) looked less grim at first glance. They found cocaine or amphetamine could help when the schedule was hard. The twist is baseline strain: their animals started with tough ratios, so the drug lifted low rates. F et al. used an easy chain, so the drug only had room to hurt.

Harris et al. (1978) add the rule: if past training made animals respond slowly, amphetamine speeds them up; if they already respond fast, it slows them down. Estradiol in F et al. may push the baseline even higher, so the same drug now looks extra harmful.

For BCBAs, the lesson is to check both biology and history before blaming the program. A client on stimulant meds or hormone therapy may need easier tasks, smaller steps, or extra practice. Drop the difficulty until accuracy returns, then rebuild. Track rate and correctness separately so you can spot when a hidden variable, not your teaching, is at fault.