1982 — 1983 |
Domino, Edward |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Joint U.S.-French Seminar On Chemistry, Pharmacology, Toxicology, Therapy and Drug Abuse Aspects of Arylcyclohexylamines @ University of Michigan Ann Arbor |
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1985 — 1992 |
Domino, Edward |
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. |
Neuropsychopharmacology of Phencyclidine @ University of Michigan At Ann Arbor
This project proposes to use electrophysiological and behavioral techniques such as brain wave measurements, single nerve cell recordings and stimulus discrimination behavior to better define the sites and mechanisms of action of phencyclidine and derivatives. A systematic evaluation of the role of behavioral and pharmacological factors in tolerance, physical dependence and withdrawal reaction to phencyclidine and possible methods of treatment will then be undertaken. The subjects of this research will be albino rats and Macaca mulatta monkeys.
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1987 |
Domino, Edward |
R13Activity Code Description: To support recipient sponsored and directed international, national or regional meetings, conferences and workshops. |
Sigma Opioid/Pcp Like Compounds as Molecular Probes @ University of Michigan At Ann Arbor
phencyclidine; molecular biology; opiate alkaloid; psychopharmacology; immunology; biochemistry; behavioral medicine; chemical structure function; toxicant interaction; travel;
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1987 — 1988 |
Domino, Edward |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Us-France Joint Workshop On Sigma Opioid/Pcp-Like Compounds as Molecular Probes in Biology, Ann Arbor, Michigan, June L987 @ University of Michigan Ann Arbor |
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1991 — 1992 |
Domino, Edward |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
U.S-France Joint Seminar: Multiple Sigma and Pcp Receptor Ligands: Mechanisms For Neural Modulation and Protection, Montpellier, France, September 1991 @ University of Michigan Ann Arbor
This award will support US participation in a US-France joint seminar on the topic of "Multiple Sigma and PCP Receptor Ligands: Mechanisms for Neural Modulation and Protection?", to be held in Montpellier, France, in September 1991. The US and French organizers are: Dr. Edward Domino, Department of Pharmacology, University of Michigan, and Dr. Jean-Marc Kamenka, Ecole Nationale Superieure de Chimie, Montpellier, France. The seminar will cover the use of sigma and PCP receptor ligands in chemistry, biochemistry, molecular biology, neurobehavioral sciences, psychopharmacology and toxicology. Their interaction with different neurotransmitters or modulators will be updated and the search for specific sigma and PCP receptor agonists and antagonists will be described. PCP and its derivatives are currently important molecular probes in many aspects of biology and are also being considered as novel therapy as antipsychotic, anticonvulsant and neural protective agents. This seminar will bring together leading experts in this rapidly moving field of study and will provide an opportunity for valuable interactions. Results of the seminar will be published and are expected to be disseminated widely in the scientific community.
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1992 — 1994 |
Domino, Edward |
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. |
Tobacco Smoking and Withdrawal On the Topographic Eeg @ University of Michigan At Ann Arbor
APPLICANT'S ABSTRACT: Tobacco smoking represents a major health problem in view of its long term harmful effects. Most tobacco users are well aware of the hazards of smoking yet they continue this life threatening habit, presumably because of their dependence upon nicotine. The specific aim of this proposed research is to determine the effects of tobacco smoking and withdrawal on the topographic electroencephalogram (EEG) and its relationship to behavioral alertness. The former is a microcomputer generated map of the electrical activity at specific regions of the brain as measured by scalp disc electrodes. Normal adult tobacco smokers of mixed sex will be recruited in groups of eight. Minority representation will be included as part of the experimental design. A controlled study will be performed in which an initial recording will be taken after zero, 1/2, 12, 24, 72 and 168 hours of abstinence from smoking. Another recording will be taken after the volunteer smokes either a zero, low or high nicotine containing research cigarette. The topographic mapping will be analyzed to determine the degree and location of specific effects of nicotine in tobacco smoking on brain activity. These EEG changes will be obtained with the eyes closed so as to be able to determine spontaneous alterations in the frequencies of alpha as well as other EEG rhythms. Behavioral alertness with the eyes closed will be measured using the subject's estimate of the number of correct unusual presentations for the oddball tones as a continuous performance task. Both the auditory evoked potential (P300) and the contingent negative variation potential in response to pressing a lever to an oddball tone will be measured and correlated with the subject's actual performance. The hypothesis of this research is that tobacco smoking will cause an increase in the frequency of brain alpha electroencephalographic activity consistent with an awake relaxed state.The cortical areas most affected will be the occipital, parietal, and central regions. Central midline alpha due to tobacco smoking is a new phenomenon which preliminary research in preparation for this grant application has already obtained, but needs more effort to document and expand to different periods of tobacco abstinence.
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1997 — 2000 |
Domino, Edward |
P01Activity Code Description: For the support of a broadly based, multidisciplinary, often long-term research program which has a specific major objective or a basic theme. A program project generally involves the organized efforts of relatively large groups, members of which are conducting research projects designed to elucidate the various aspects or components of this objective. Each research project is usually under the leadership of an established investigator. The grant can provide support for certain basic resources used by these groups in the program, including clinical components, the sharing of which facilitates the total research effort. A program project is directed toward a range of problems having a central research focus, in contrast to the usually narrower thrust of the traditional research project. Each project supported through this mechanism should contribute or be directly related to the common theme of the total research effort. These scientifically meritorious projects should demonstrate an essential element of unity and interdependence, i.e., a system of research activities and projects directed toward a well-defined research program goal. |
Effects of Nicotine On Cerebral Blood Flow/Metabolism @ University of Michigan At Ann Arbor
There are three specific aims to this grant proposal. These are to determine the effects of nicotine in tobacco smoking amounts on (1) regional blood flow and (2) regional glucose metabolism in the brains of adult cigarette smokers (3) males and females. Only cigarette smokers will be studied. State-of-the-art imaging technology using positron emission tomography is available and ready to use with equipment already paid for at no extra cost to this grant. Nicotine will be administered by smoking a standardized research cigarette, as well as a nasal spray of a pure solution in order to determine whether the effects observed are due to nicotine alone or nicotine plus other chemicals in tobacco smoke. in addition, blood nicotine and cotinine concentrations will be measured and correlated with the induced functional brain changes. The cerebral blood flow study will compare regional cerebral blood flow following nicotine cigarettes and nicotine spray in 24 (12 male, 12 female) cigarette smokers, in a cross over, repeated measures design. Each subject will undergo two PET sessions scheduled at least one month apart. During each PET session five [15O] water scans will be run. During each of the two PET sessions the first scan (baseline) will be followed by a scan immediately following inhalation of 5% CO2. The third scan will follow either nicotine placebo nasal spray or placebo cigarette administration, the fourth scan will follow either a nicotine cigarette/nasal spray administration, and the fifth scan will follow a repeat nicotine cigarette/nasal spray administration. These functional brain measures will be correlated with arterial and venous blood concentrations of nicotine measured by HPLC. The cerebral metabolic rate study will require that 24 (12 male, 12 female) tobacco smokers undergo two PET scans following injection with [18F]fluorodeoxyglucose, half of the subjects will be randomized to receive nicotine nasal spray and placebo nicotine nasal spray during two separate PET sessions scheduled at least a month apart. The other half will receive nicotine cigarettes and placebo cigarettes. The findings of this research will increase understanding of the effects of nicotine on the brains of normal male and female adults. This new information will make it easier to help understand why tobacco smoking is reinforcing and why it is so difficult to quit. the research proposed is both timely and accomplishable. Such information could lead to novel treatments for nicotine dependence by identifying the involvement of pertinent brain regions as well as possible pathways. This could set the stage for the study of nicotine effects in persons with cofactors for smoking, such as attention deficit disorder or mood disorders.
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1997 — 2001 |
Domino, Edward |
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. |
Nicotine Effects On Cerebral Blood Flow and Metabolism @ University of Michigan At Ann Arbor
DESCRIPTION: (Applicant's Abstract) There are three specific aims to this grant proposal. These are to determine the effects of nicotine in tobacco smoking amounts on (1 ) regional blood flow and (2) on regional glucose metabolism in the brains of adult cigarette smokers and (3) on males and females. Only cigarette smokers will be studied. State of the art imaging technology using positron emission tomography is available and ready to use with equipment already paid for at no extra cost to this grant. Nicotine will be administered by smoking a standardized research cigarette, as well as a nasal spray of a pure solution in order to determine whether the effects observed are due to nicotine alone or nicotine plus other chemicals in tobacco smoke. In addition, blood nicotine and cotinine concentrations will be measured and correlated with the induced functional brain changes. The cerebral blood flow study will compare regional cerebral blood flow following nicotine cigarettes and nicotine spray in 24 (12 male, 12 female) cigarette smokers, in a cross over, repeated measures design. Each subject will undergo two PET sessions scheduled at least one month apart. During each PET session five H-2-15-O scans will be run. During each of the two PET sessions, the first scan (baseline) will be followed by a scan immediately following inhalation of 5% CO2. The third scan will follow either nicotine placebo nasal spray or placebo cigarette administration, the fourth scan will follow a repeat nicotine cigarette/nasal spray administration, and the fifth scan will follow a repeat nicotine cigarette/nasal spray administration. These functional brain measures will be correlated with arterial and venous blood concentrations of nicotine measured by HPLC. The cerebral metabolic rate study will require that 24 (12 male, 12 female) tobacco smokers undergo two PET scans following injection with [18F]flurodexoxyglucose. Half of the subjects will be randomized to receive nicotine nasal spray and placebo nicotine nasal spray during two separate PET sessions scheduled at least a month apart. The other half will receive nicotine cigarettes and placebo cigarettes. The findings of this research will increase understanding of the effects of nicotine on the brains of normal male and female adults. This new information will make it easier to help understand why tobacco smoking is reinforcing and why it is so difficult to quit. The research proposed is both timely and accomplishable. Such information could lead to novel treatments for nicotine dependence by identifying the involvement of pertinent brain regions as well as possible pathways. This could set the stage for the study of nicotine effects in persons with cofactors for smoking, such as attention deficit disorder or mood disorders.
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2006 — 2008 |
Domino, Edward |
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. |
Effects of Nicotine On Human Cerebral Transmitters @ University of Michigan At Ann Arbor
[unreadable] DESCRIPTION (provided by applicant): There are three specific aims to this proposal. These are to determine the effects of 1) smoking denicotinized and average nicotine research cigarettes and tobacco smoking equivalent doses of intravenous nicotine (2) and (3) on regional cerebral release of dopamine and endogenous mu opioids in adult male and female tobacco smokers. State of the art positron emission tomography (PET) will be used. To date, data in humans that tobacco smoking releases brain dopamine are very limited and unclear. There are no data that tobacco smoking releases endogenous opioids in human brain. Our preliminary data in six subjects demonstrate proof of concept, but a larger number of tobacco smokers needs to be studied. The functional brain measures will be correlated with venous concentrations of nicotine measured by HPLC. The regional cerebral release of dopamine and endogenous opioids will be measured indirectly as competitive displacement of [11C]raclopride and [11C]carfentinil, respectively. Two separate groups of 36 subjects each will be scheduled for two PET sessions to be performed within a one-week period. All subjects will be run in a similar counterbalanced design. The findings resulting from this research will increase understanding of the effects of nicotine on the brains of normal male and female adult smokers. This information will be important to determine in humans the specific brain areas involved in the reinforcing actions of nicotine and tobacco smoking. This research will provide direct proof of basic neuroscience studies, which indicate nicotine releases neurotransmitters such as dopamine and endogenous opioids. [unreadable] [unreadable] [unreadable]
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