Neural mechanisms of drug stimuli: experimental approaches

Drug discrimination methodology affords a behavioral end point that reflects actions of a drug at the cellular level. The stimulus control of behavior by drugs of many pharmacological classes satisfies criteria for a receptor-mediated phenomenon. Within many classes of drugs, order of relative of potency for discriminative effects correlates highly with the order of potency of the drugs in other procedures that involve interactions with a defined population of receptors. Examples include the morphine-like opioids and the benzodiazepines. Specific competitive antagonists are of paramount importance for defining neuronal substrates that subserve the discriminative effects of a drug. Quantitative pharmacological approaches can be used not only to define the receptor mediating the discriminative effects of a drug but also to assess the intrinsic activity of the drug at the receptor. The primary site of stimulus control of behavior by most drugs can be shown by indirect and direct means to be of central rather than peripheral origin; however, neuronanatomical localization of specific sites of drug action remains elusive. Attention is starting to be focused on endogenous neuropeptides, their discriminative stimulus properties and potential role in modulating discriminative effects of drugs. Some of the most important contributions of drug discrimination methodology may arise in the rapidly emerging area of peptide neuropharmacology.