When an abused drug is self-administered it produces internal stimuli in the user of which the user is often aware. We refer to these effects in humans as the """"""""subjective effects"""""""" of the drug. One way in which behavioral pharmacologists have studied these internal stimuli in animal models has been to establish them as discriminative stimuli. Responses can be scheduled to occur or not occur in the presence or absence of these internal drug stimuli by differentially reinforcing responding. These drug discrimination procedures have been used to study the behavioral consequences of a number of effects of drugs at the cellular level of the brain including receptor binding, neurotransmitter depletion, and many others. Despite the widespread usage of drug discrimination procedures, there are many questions about the procedure that have not been answered. For example, there are arguments about whether or not drug discrimination gradients are quantal or graded. It is not known if the discrimination between two different drugs differs from the discrimination between the presence and absence of a single drug. Although the experience of an organism with other drugs has been shown to be an important determinant of many drug effects, such historical factors have received little attention in drug-discrimination research. The ability of animals to learn complex drug discriminations has also received little attention and there are almost no studies in the literature that systematically compare the effects of drugs as discriminative stimuli with their effects on other behaviors. The proposed research would fill this gap by determining how reinforcement schedules and drug discrimination training history affect the discriminative stimulus properties of drugs. Experiments would also be conducted to develop new procedures for studying and interpreting complex drug discriminations and for comparing the effects of drugs as discriminative stimuli to their effects on animal models of anxiety, memory and other important behaviors. These experiments will provide fundamental new information about the drug discrimination process that should greatly add to our knowledge of how the stimulus properties of drugs contribute to their abuse.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Project (R01)
Project #
Application #
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Schnur, Paul
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Arkansas for Medical Sciences
Schools of Medicine
Little Rock
United States
Zip Code
Wessinger, William D; Li, Mi; McMillan, Donald E (2011) Drug discrimination in pigeons trained to discriminate among morphine, U50488, a combination of these drugs, and saline. Behav Pharmacol 22:468-79
McMillan, D E; Wessinger, William D; Li, Mi (2009) Effects of drugs and drug combinations in pigeons trained to discriminate among pentobarbital, dizocilpine, a combination of these drugs, and saline. J Exp Anal Behav 92:387-412
Hendrickson, Howard P; Hardwick, William C; McMillan, D E et al. (2008) Bioavailability of (+)-methamphetamine in the pigeon following an intramuscular dose. Pharmacol Biochem Behav 90:382-6
Frawly, Kristyn; McMillan, Donald E (2008) Effects of gamma-hydroxybutyrate on punished responding in pigeons. Behav Pharmacol 19:77-9
Daniels, J R; Wessinger, W D; Hardwick, W C et al. (2006) Effects of anti-phencyclidine and anti-(+)-methamphetamine monoclonal antibodies alone and in combination on the discrimination of phencyclidine and (+)-methamphetamine by pigeons. Psychopharmacology (Berl) 185:36-44
Li, Mi; Wessinger, William D; McMillan, D E (2005) Effects of amphetamine-CNS depressant combinations and of other CNS stimulants in four-choice drug discriminations. J Exp Anal Behav 84:77-97
McMillan, D E; Hardwick, W C; Li, Mi (2002) Drug discrimination under concurrent variable-ratio variable-ratio schedules. J Exp Anal Behav 77:91-104
McMillan, D E; Li, Mi (2002) The discrimination of drug mixtures using a four-choice procedure in pigeons. Psychopharmacology (Berl) 164:207-13
McMillan, D E; Li, M (2001) LAD rats learn a three-key drug discrimination more rapidly and achieve a higher level of performance than HAD rats. Behav Pharmacol 12:545-8
McMillan, D E; Li, M; Hardwick, W C (2001) Schedule control of quantal and graded dose-effect curves in a drug-drug-saline discrimination. Pharmacol Biochem Behav 68:395-402

Showing the most recent 10 out of 61 publications