Rationale One important technique in behavioral pharmacology is to train laboratory animals to discriminate between a psychoactive drug effect and a nondrug condition. Tests with different drugs have identified several categories of drugs that have different discriminable effects. Objectives The two authors describe and discuss the early research on discriminable effects of sedative and hallucinogenic drugs and their acquaintance with each other at Yale University prior to their early and frequent publications on discriminable drug effects. Herb Barry studied sedative drugs primarily and Jim Appel studied hallucinogenic drugs. Results Sedative drugs include ethyl alcohol, barbiturates, and benzodiazepines. Their discriminable effects are largely attributable to the activation of an inhibitory neurotransmitter, γ-amino butyric acid. Alcohol has the most pervasive effect in accordance with the high dose required to alter behavior. Hallucinogenic drugs include lysergic acid diethylamide and mescaline. They increase the activity of the neurotransmitter 5-hydroxytryptamine and, perhaps, dopamine in the central nervous system (CNS). In spite of their relatively low concentrations in the brain, both of these neurotransmitters have many important behavioral effects.Conclusions Various sedative drugs cause a discriminable decrease in the function of the CNS. Different types of sedatives can be discriminated from each other. Indole and phenylethylamine hallucinogens have potent discriminative stimulus properties, which are related to the actions of biogenic amine neurotransmitters in the CNS.Keywords Discriminative stimulus . Sedatives . Hallucinogens . GABA . Serotonin . Dopamine . Laboratory animals . History . Operant . Alcohol A drug that changes the action of the central nervous system (CNS) can be a strong discriminative stimulus that alters behavior such as the choice between different responses. The most prominent type of discriminative stimulus is a sensory signal. Examples are a traffic light received by the eyes and a warning siren received by the ears. A drug effect that alters the action of the CNS is a discriminable change in physiological state or in "consciousness." An individual can, therefore, learn different responses depending on whether or not the drug is acting on the CNS.Research on discriminable drug effects constitutes a portion of the interdisciplinary field of preclinical psychopharmacology. Potentially therapeutic or nontherapeutic drugs that alter behavior are tested in laboratory animals. An alternative term for this research field is behavioral pharmacology.After a discriminable drug effect is trained, "substitution" or "generalization" tests determine whether the effect of another drug or of a different condition resembles the effect of the initial drug. Different conditions can include the initial drug after a lower or higher dose ("doseresponse" test), after a shorter or longer time interval ("time-response" test), or after a different route of Psychopharmacology
