1985 — 1989 |
Overton, Donald A |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Basic Mechanisms of State Dependent Learning
Experiments are proposed in four areas relating to the stimulus properties of drugs. Project 1 seeks to improve the utility of the drug discrimination procedure so as to enhance its utility as a preclinical research method by identifying training procedures which will yield results more accurately representational of underlying drug effects than do the results of present drug discrimination procedures. Project 2 seeks to identify the type of mechanism responsible for state dependent learning. The threshold dosages that are required to produce drug discriminations and state dependent learning will be determined. Comparison of these thresholds should demonstrate whether or not sensory events underlie both phenomena. Project 3 will investigate the degree to which behaviors learned in the no drug condition become contingent upon interoceptive cues present in that condition. Theory and experimental results presently disagree on this issue, which leads to incorrect interpretation of experimental results and hinders attempts to improve the drug discrimination procedure. Project 4 will investigate whether drugs can become conditioned stimuli in classical conditioning paradigms, thus acquiring conditioned reactions that may augment or interfer with the usual effects of the drugs. Experiments are proposed to determine the ease of formation of such conditioned reactions to drugs, the variety of situations in which they occur, and the rapidity with which they extinguish. A total of ten separate experiments are proposed.
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1985 — 1988 |
Overton, Donald A |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
New Behavioral Methods For Categorizing Abused Drugs
This application proposes five types of experiments. All are intended to develop improved behavioral methods for categorizing abused drugs, and/or for determining the abuse liability of drugs. All are based on the drug discrimination technique. Project 1 is applied in nature. It seeks to develop high specificity assay techniques which can determine whether newly developed antianxiety drugs produce subjective effects more like those of highly abused depressants such as ethanol, or more like those of less abused drugs such as diazepam. If successful, the method will provide a new preclinical method for predicting the abuse liability of anxiolytic drugs. Project 2 will investigate the degree to which behaviors learned in the no drug condition become contingent upon interoceptive cues present in that condition. Theory and experimental results presently disagree on this issue, which leads to incorrect interpretation of experimental results and hinders attempts to improve the drug discrimination procedure. Project 3 will test for the occurrence of stimulus masking in the drug discrimination preparation, to determine whether this is a frequent or rare phenomenon. Project 4 consists of three separate experiments. The first will calibrate the substitution test procedure by determining the minimum degree of cue overlap between the sensory effects of training and test drugs that can be detected by the procedure, and the percentage of drug-lever responses that occur with higher degrees of overlap. The next experiment will test for the occurrence of cue overlap between the sensory effects of drugs which produce pharmacologically dissimilar actions. The third experiment will determine the degree to which the specificity of the DD paradigm varies as a function of the training dosage employed. Project 5 will investigate the utility of several new multiple-drug training procedures which are designed to allow rapid measurements of the subjective effects of drugs. A total of 14 separate experiments are proposed using rats and pigeons as subjects.
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1989 — 1990 |
Overton, Donald A |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Conditioning Mechanisms Underlying Alcohol Abuse
To improve our understanding of the mechanisms underlying alcohol abuse, experiments are proposed to test the possibility that classical conditioning, with the effects of ethanol acting as hte conditioned stimulus (CS), can temporarily modify the effects of alcohol, and hence the likelihood of its abuse. The first experiment replicates a previous experiment showing that a low dose (first drink) of ethanol could, after classical conditioning, induce an ethanol-opposite effect on body temperature. Experiments 2 and 3 extend this study by investigating the effects of partial reinforcement of the CS, and of temporal parameters in the conditioning paradigm. Experiment 4 tests whether drugs other than ethanol can act as CSs, and is a necessary precursor to Experiment 5 which tests whether the subjective (sensory) effects of ethanol withdrawal can be established as conditioned responses (CRs) to drug CSs. Experiment 6 investigates interactions between the effects of anxiety and those of ethanol, by testing whether fear induced by pentylenetetrazol can become a CS which induces an ethanol-opposite CR. The experiments are designed to elucidate the mechanisms which initiate and maintain the abuse of alcohol, and specifically the role of drugs as conditioned stimuli.
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1 |
1989 — 1991 |
Overton, Donald A |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Modification of Drug Effects by Conditioning Procedures
To improve our understanding of the causes of drug abuse, experiments are proposed to test the possibility that one drug can acquire the ability to elicit the \effects normally produced by a second drug as the result of classical conditioning procedures. More specifically, the studies investigate whether administration of a low dose of one drug can be made to elicit the sensory effects characteristic of withdrawal from a different drug (or craving for the second drug). A series of six experiments using rats is proposed. The first of these replicates a previously demonstrated conditioning effect using body temperature as the dependent variable. Subsequent experiments incrementally shift the focus of attention into the domain of sensory effects of drugs. The final experiment tests whether a low dose of ethanol can, after classical conditioning procedures, evoke the sensory effects normally produced by withdrawal form narcotics.
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1989 — 1991 |
Overton, Donald A |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
New Behavioral Methods For Categorizing Abused Drugs.
This application proposes experiments intended to develop improved behavioral methods for categorizing abused drugs, and/or for determining the abuse liability of drugs. All are based on the drug discrimination technique. Experiment 1 will test for the occurrence of stimulus masking in the drug discrimination preparation, to determine whether this is a frequent or rare phenomenon. Experiment 2 will test for the occurrence of cue overlap between the sensory effects of drugs which produce pharmacologically dissimilar actions. Experiment 3 will determine the degree to which the specificity of the DD paradigm varies as a function of the training dosage employed. Experiment 4 involves training with a mixture of two different drug cues in order to determine whether perception of drug stimuli is analytic or synthetic in nature, and to investigate individual differences between animals i cue usage when more than one cue is available. Experiment 5 investigates the degree to which the drug stimuli present at the time of onset of drug actions differ from those which occur later. Experiments 6-8 will investigate the utility of a novel multiple-drug training procedure which is designed to allow concurrent discrimination of several training drugs. A total of 8 separate experiments are proposed using rats and pigeons as subjects.
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1 |
1993 — 1995 |
Overton, Donald A |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Alcohol Abuse and Conditioned Drug Effects |
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