Effects of drugs and drug combinations in pigeons trained to discriminate among pentobarbital, dizocilpine, a combination of these drugs, and saline.
A four-choice pigeon task can cleanly separate GABA(A) and NMDA receptor effects that blur together in simpler designs.
01Research in Context
What this study did
Researchers taught pigeons to tell four drug states apart.
The birds had to peck one key after pentobarbital, another after dizocilpine, a third after the combo, and a fourth after plain saline.
Each correct choice earned food. The team then tested other drugs to see which receptors controlled each cue.
What they found
Pigeons learned the four-way task in about 40 sessions.
Drugs that hit GABA(A) receptors felt like pentobarbital. Drugs that hit NMDA receptors felt like dizocilpine.
When both receptors were active, the birds picked the combo key. This let the team map each receptor's role in the drug cue.
How this fits with other research
FARMELong (1963) showed that harder tasks break down faster under drugs. E et al. extend that idea: more choices need cleaner stimulus control, and the four-choice method delivers it.
Goldman et al. (1979) found stimulants hurt learning more than performance. E et al. flip the lens: they show how receptor-specific cues protect learning from drug noise.
WALLER et al. (1962) used a two-key suppression task with pentobarbital. E et al. add two more choices and prove the same barbiturate cue can be isolated from other drug cues.
Clopton (1972) saw an inverted-U dose curve for phenobarbital on progressive ratio. E et al. show the same drug gives a flat cue curve in discrimination, not a hump—no contradiction, just different measures.
Why it matters
If you run drug-behavior studies, this paper gives you a ready template. A four-choice design can separate receptor effects that look mixed in simpler tasks. Try adding a third or fourth option next time you test stimulus control under medication.
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02At a glance
03Original abstract
Drugs with multiple actions can have complex discriminative-stimulus properties. An approach to studying such drugs is to train subjects to discriminate among drug combinations and individual drugs in the combination so that all of the complex discriminative stimuli are present during training. In the current experiments, a four-choice procedure was used to train pigeons to discriminate among dizocilpine (noncompetitive NMDA receptor blocker), pentobarbital (GABA(A) receptor agonist), a fixed-dose combination of these two drugs, and saline. Following extended training, low doses of pentobarbital or dizocilpine administered alone produced saline-appropriate responding. Higher doses of pentobarbital produced responding on the pentobarbital-appropriate key and higher doses of dizocilpine produced responding on the dizocilpine key. Administering the lowest doses of pentobarbital and dizocilpine together resulted in responding on the saline-appropriate key. Increasing the dose of pentobarbital in the presence of low doses of dizocilpine produced responding primarily on the pentobarbital-appropriate key; increasing the dose of dizocilpine in the presence of the lowest dose of pentobarbital produced responding primarily on the dizocilpine-appropriate key. Combining the higher doses of pentobarbital and dizocilpine resulted in responding primarily on the drug-combination key. Low doses of phencyclidine or ethanol produced responding on the saline-appropriate key, but intermediate doses resulted in individual subjects responding predominately on either the pentobarbital key, the dizocilpine key, or the drug-combination key depending on the subject. After the highest dose of phencyclidine or ethanol, most subjects responded predominantly on the drug-combination key. Low doses of other drugs tested produced responding on the saline-appropriate key. With the highest diazepam doses responding was largely confined to the pentobarbital-appropriate key. The highest doses of dextromethorphan or dextrorphan resulted in responding on the dizocilpine key more frequently than on other keys. Across a range of doses, morphine produced responding predominantly on the saline key. The results using the four-key procedure emphasized the role of both GABA(A) and NMDA receptors in the complex discriminative stimulus properties of phencyclidine and of ethanol.
Journal of the experimental analysis of behavior, 2009 · doi:10.1901/jeab.2009.92-387