Effects of drugs and drug combinations in pigeons trained to discriminate among pentobarbital, dizocilpine, a combination of these drugs, and saline.

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.