1986 — 1988 |
Samson, Herman H |
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. |
Models of Drinking Initiation--Behavioral Study @ University of Washington
A series of animal studies are proposed to examine the consequences of different drinking initiation procedures upon later ethanol use. In prior experiments in our laboratory, three distinct theoretical models have been developed that all result in successful ethanol reinforced behavior. However, no attempts have been made to determine if any of these different models result in differential drinking in chronic or stress situations. As well, the role of alcohol preference has not been examined in these models. The proposed experiments will test these hypothesis and use the results to make predictions concerning adolescent drinking. Prevention models could be suggested that would be aimed at reducing risk that may result from certain types of drinking initiation experiences.
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0.955 |
1989 |
Samson, Herman H |
R03Activity Code Description: To provide research support specifically limited in time and amount for studies in categorical program areas. Small grants provide flexibility for initiating studies which are generally for preliminary short-term projects and are non-renewable. |
Ethanol Reinforcement in Brain Dopamine @ University of Washington
Determining the mechanisms which regulate ethanol drinking in the brain will provide greater insight into the various factors which can lead to abuse. If we are to develop better methods of treating alcohol abuse and alcoholism, this knowledge seems essential. How ethanol functions as a reinforcer is still unclear, but recent studies would indicate that it may function through mechanisms not unsimiliar to other well known reinforcing drugs. To better understand how ethanol functions as a reinforcer, the application of the state-of-the-art neuroscience techniques is required. The techniques of brain dialysis and voltammetry are rapidly gaining acceptance as the primary procedures to be used to monitor the release of various neurotransmitters in behaving animals. this proposal requests funds for the Principal Investigator to learn these techniques and then apply them in an animal model of ethanol self-administration. Only by having the opportunity to spend time with the Hosts, who are experts n the techniques, can the Principal Investigator gain the knowledge necessary to apply them appropriately.
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0.955 |
1989 — 1993 |
Samson, Herman H |
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. |
Models of Drinking Initiation--Behavorial Study @ University of Washington
Understanding the factors that regulate ethanol intake are critical for effective treatments of alcohol abuse and alcoholism. Interactive factors already established being involved included genetic sensitivity, ethanol's reinforcing capability, and environmental conditions. One critical component controlling drinking may be the nature of ethanol initiation. That initiation processes alter later ethanol drinking has been the working hypothesis of our prior grant period and remains a part of this competing renewal. In our previous grant period we demonstrated that initiated animals consume more ethanol than non-initiated animals. Initiation by means of a sucrose-fading procedure results in greater intakes than does initiation using a secondary conditioning model. Thus, different initiation procedures result in different ethanol intakes. We showed that ethanol intake following initiation was independent of food and fluid intake. When environmental conditions were altered, ethanol intakes increased. However, animals initiated with the sucrose-fading procedure increased their intakes greater than did the secondary conditioning rats. At no time in these studies was excessive drinking found. In an independent study either initiation procedure was shown to overcome a genetic selection for ethanol aversion (NP rats) and resulted in these rats actively working to obtain 40% ethanol. These proposal builds on the findings of the previous grant. Studies are planned to examine the relation of environmental changes upon ethanol intake following initiation. Both the response requirement to obtain ethanol and the time during the day fin which ethanol can be obtained will be varied. f Also, the concentration of ethanol presented will be varied. In a second set of experiments, the relation of initiation procedures and genetic selection will be examined. Animals from the Indiana-preferring and non-preferring strains will be initiated to drink ethanol. They will then be tested in a chronic ethanol drinking condition to determine the pattern and nature of their ethanol consumption. These studies will increase our understanding of ethanol drinking in complex situations and of the regulation of that drinking by alteration of both genetic and environmental factors in addition to the process by which ethanol ingestion is initiated.
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1 |
1989 — 1993 |
Samson, Herman H |
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. |
Oral Ethanol Drinking and Cns Dopamine-Gaba Systems @ University of Washington
Understanding the processes which control ethanol self- administration is of primary importance in eventual treatment and prevention of alcohol abuse and alcoholism. The nature and biological mechanisms of ethanol's reinforcing properties are central to the overall understanding of this intake control. Recently, a neural basis for reward has been postulated to be important for a variety of abused drugs. The role which this neural system plays in ethanol reinforcement and intake has yet to be thoroughly explored. The proposed studies will begin to examine the role which this brain reward system may play in ethanol self- administration. A biological model will be used in which oral ethanol self- administration is initiated without the need for food or water deprivation. When the animals are orally self-administering ethanol, a variety of agonists and antagonists active at either dopaminergic, GABAergic or benzodiazepinergic receptor sites will be injected directly into specific brain loci to determine their affect on self-administration. The drugs to be tested are halo- peridol, apomorphine, muscimol, bicuculine, chlordiazepoxide and an inverse benzodiazepine agonist. The brain areas of interest are the nucleus Accumbens, caudate putamen, the ventral tegmental area (A10), the substantia nigra and the ventral pallidum. Control animals, orally self-administering either sucrose only or concurrently administering ethanol and sucrose, will also be examined using the same procedures used for ethanol self-admini- stration. Comparison of these three self-administration conditions will allow for an initial determination of the role which the postulated brain reward system may play in ethanol self- administration.
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1 |
1992 — 2003 |
Samson, Herman H |
K05Activity Code Description: For the support of a research scientist qualified to pursue independent research which would extend the research program of the sponsoring institution, or to direct an essential part of this research program. R37Activity Code Description: To provide long-term grant support to investigators whose research competence and productivity are distinctly superior and who are highly likely to continue to perform in an outstanding manner. Investigators may not apply for a MERIT award. Program staff and/or members of the cognizant National Advisory Council/Board will identify candidates for the MERIT award during the course of review of competing research grant applications prepared and submitted in accordance with regular PHS requirements. |
Behavioral and Physiological Control of Ethanol Drinking @ Wake Forest University Health Sciences
The relationship between environmental and genetic factors in the regulation of alcohol consumption, while often cited as important, are not well understood. While a number of studies have examined the effects of various environmental factors on alcohol consumption, only a few of these have attempted to determine how these factors might interact with genetic factors. During the last grant period, we have found that several behavioral factors can impact ethanol consumption and that several of these factors interact with each other. Depending on the type of introduction (initiation) to alcohol, the amount, concentration, and cost of the ethanol and time/day it is available all effect intake. The most important finding has been that intake appears to be mostly regulated by the number of discrete drinking bouts which occur during a day and not by the size of these individual bouts. This appears true for both nonselected rats as well as for both the Indiana P and NP rat. The proposed studies will expand on these studies by examining the effects of initiation and an environmental variable upon drinking patterns of several lines of rats. By using the same behavioral procedure, in the same laboratory across several lines of selectively bred animals who differ in their alcohol preference, we hope to be able to address the question of the interaction between these genetic selections and environmental factors which are known to impact ethanol consumption. An additional set of studies is proposed to continue to explore added models of drinking initiation, with the goal of providing other models of alcohol self-administration which may better resemble excessive drinking patterns.
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1 |
1993 — 1994 |
Samson, Herman H |
R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Voltammetric Dopamine Measurement in Ethanol Reinforcemt
The understanding of how ethanol's reinforcing properties function within the central nervous system has been considered as a potential key to the development of new and more effective pharmacotherapeutic interventions for alcohol abuse and alcoholism. In this exploratory/developmental grant, the use of In Vivo voltammetry will be implemented to examine the role of the mesolimbic dopamine system to ethanol reinforcement, in rats who are orally self-administrating ethanol. The main goal of this project is to develop the voltammetry technique in animals that have been initiated to selfadminister ethanol in an operant paradigm. To accomplish these ends, several technical aspects of applying the voltammetry technique to non-anesthetized animals will have to be integrated into the PI's laboratory. While there are no apparent major technical obstacles, the application of voltammetry in this manner is in its early stages of development in the field of neurosciences. However, the potential abilities of this technique to provide critical new information about how the mesolimbic dopamine system may be involved in the regulation of ethanol consumption makes the development of this specific application most appropriate to the goals of this program announcement.
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1 |
1994 — 1996 |
Samson, Herman H |
K05Activity Code Description: For the support of a research scientist qualified to pursue independent research which would extend the research program of the sponsoring institution, or to direct an essential part of this research program. |
Behavioral &Physiological Control of Ethanol Drinking |
1 |
1994 — 1998 |
Samson, Herman H |
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. R37Activity Code Description: To provide long-term grant support to investigators whose research competence and productivity are distinctly superior and who are highly likely to continue to perform in an outstanding manner. Investigators may not apply for a MERIT award. Program staff and/or members of the cognizant National Advisory Council/Board will identify candidates for the MERIT award during the course of review of competing research grant applications prepared and submitted in accordance with regular PHS requirements. |
Behavioral and Physiological Control of Drinking |
1 |
1994 — 1999 |
Samson, Herman H |
T32Activity Code Description: To enable institutions to make National Research Service Awards to individuals selected by them for predoctoral and postdoctoral research training in specified shortage areas. |
Multi-Disciplinary Training in the Biology of Alcoholism |
1 |
1994 — 2002 |
Samson, Herman H |
P50Activity Code Description: To support any part of the full range of research and development from very basic to clinical; may involve ancillary supportive activities such as protracted patient care necessary to the primary research or R&D effort. The spectrum of activities comprises a multidisciplinary attack on a specific disease entity or biomedical problem area. These grants differ from program project grants in that they are usually developed in response to an announcement of the programmatic needs of an Institute or Division and subsequently receive continuous attention from its staff. Centers may also serve as regional or national resources for special research purposes. 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. |
Oral Ethanol Drinking and Cns Dopamine/Gaba Systems
Over the last several years we have been exploring the role of the mesolimbic dopamine system in ethanol reinforcement. Our main hypothesis has been to determine, using site specific microinjection of agonists and antagonists within this system, the effects upon ethanol self- administration in an operant paradigm. Based on these findings, we know the complex interactions between these pathways and the potential specific entry point(s) for ethanol's access to these systems remains to be determined. The work proposed over the next five years will address these issues. There are 4 specific aims. Using a new behavioral technique which we have recently developed, Aim 1 we will assess the issues of specificity of site specific microinjections for ethanol reinforcement using a multiple schedule approach. Aim 2 will examine, using the same procedures, the role of the NMDA and 5HT3 receptors within this pathway to determine if they are involved with ethanol's access to this system. In Aim 3, we will use dual site microinjections to produce multiple changes within the system, in an attempt to better understand the dynamics of this system. In Aim 4, we will use another new behavioral technique, the chain schedule, to examine the role of this system in appetitive versus consummatory components of the ethanol self- administration bout. Taken together, these studies will provide more complete information as to the function of the mesolimbic mesocortical system in the control of ethanol drinking.
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1 |
1999 — 2002 |
Samson, Herman H |
P50Activity Code Description: To support any part of the full range of research and development from very basic to clinical; may involve ancillary supportive activities such as protracted patient care necessary to the primary research or R&D effort. The spectrum of activities comprises a multidisciplinary attack on a specific disease entity or biomedical problem area. These grants differ from program project grants in that they are usually developed in response to an announcement of the programmatic needs of an Institute or Division and subsequently receive continuous attention from its staff. Centers may also serve as regional or national resources for special research purposes. |
Center For the Neurobehavioral Study of Alcohol @ Wake Forest University Health Sciences
The ability of alcohol (ethanol) to produce internal stimuli that direct appropriate behavior (i.e., discriminative stimuli) and maintain ethanol consumption (i.e., reinforcing stimuli) are fundamental processes postulated to be important for both normal drinking and excessive chronic alcohol use. However, how these ethanol stimulus effects are mediated within the central nervous system remains unclear. Work done by members of the proposed Center have elucidated several candidate neurobehavioral systems but a continued coordinated effort is needed to provide for the integration of the data from the molecular to the behavioral level of analysis. Using this already developed alcohol research team, the goals of the Center can be achieved. The Specific Aims are: 1. Provide an integrated, multi-disciplinary approach to study ethanol's discriminative and reinforcing stimulus effects. 2. Provide a national resource for the dissemination of research findings and training in the area of neurobehavioral analysis of ethanol's stimulus effects related to alcohol abuse and alcoholism. These aims are to be accomplished through the functions of an Administrative, Animal and Pilot Cores, and 5 projects which range from the molecular through the cellular to the behavioral levels of analysis.
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0.96 |
1999 — 2002 |
Samson, Herman H |
P50Activity Code Description: To support any part of the full range of research and development from very basic to clinical; may involve ancillary supportive activities such as protracted patient care necessary to the primary research or R&D effort. The spectrum of activities comprises a multidisciplinary attack on a specific disease entity or biomedical problem area. These grants differ from program project grants in that they are usually developed in response to an announcement of the programmatic needs of an Institute or Division and subsequently receive continuous attention from its staff. Centers may also serve as regional or national resources for special research purposes. |
Core--Animal
The primary function of the animal core is provide animals trained either in an ethanol-water discrimination task or to self-administer ethanol. These two animal models form the basis upon which the Center will approach the Specific Research Aims. Drs. Grant and Samson will oversee this core, with two full time technicians responsible for daily operation. The primary value of the core, besides reducing the total cost of animal preparation, is the ability to provide uniform training of the animals to all Center projects.
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