| 1985 — 1997 |
Groves, Philip M |
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. |
Mechanisms of Action of Drugs of Abuse--Amphetamine @ University of California San Diego
This application seeks renewal of research support for five years to study the sites and mechanisms of action of psychomotor stimulant drugs, including amphetamine and cocaine. Experiments are proposed to determine the mechanisms underlying alterations in catecholaminergic and non-catecholaminergic neuronal terminal excitability, including an analysis of the influence of cocaine on catecholaminergic terminal excitability and whether changes in terminal excitability of dopaminergic neurons in the rat brain occur in the chronically implanted, behaving animal. An attempt will be made to collect converging evidence regarding the identity and postsynaptic target of dopaminergic synapses made in neostriatum and to assess the relation of dopaminergic synapses made in neostriatum to its compartmentalization into the dopaminergic islandic or striosomal and matrix compartments. Further experiments are proposed to assess the consequences of amphetamine administration on neuronal activity in neostriatal targets such as pars reticulata of substantia nigra and globus pallidus. Finally, we will continue to assess the anatomical and pathological consequences of amphetamine and cocaine administration on the rat brain using tyrosine hydroxylase immunocytochemistry, the Fink-Heimer method for identifying degeneration in caudate nucleus and cerebral cortex, and biochemical analysis of potential monoamine depletions from these sites.
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| 1985 — 2001 |
Groves, Philip M |
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. |
Novel Modes of Action of Abused Drugs @ University of California San Diego |
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| 1987 — 1994 |
Groves, Philip M |
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. |
Training Program-Basic Science Foundations of Psychiatry @ University of California San Diego |
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| 1988 — 1992 |
Groves, Philip M |
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. |
Mechanisms of Action of Drugs of Abuse Amphetamine @ University of California San Diego
This application seeks renewal of research support for five years to study the sites and mechanisms of action of psychomotor stimulant drugs, including amphetamine and cocaine. Experiments are proposed to determine the mechanisms underlying alterations in catecholaminergic and non-catecholaminergic neuronal terminal excitability, including an analysis of the influence of cocaine on catecholaminergic terminal excitability and whether changes in terminal excitability of dopaminergic neurons in the rat brain occur in the chronically implanted, behaving animal. An attempt will be made to collect converging evidence regarding the identity and postsynaptic target of dopaminergic synapses made in neostriatum and to assess the relation of dopaminergic synapses made in neostriatum to its compartmentalization into the dopaminergic islandic or striosomal and matrix compartments. Further experiments are proposed to assess the consequences of amphetamine administration on neuronal activity in neostriatal targets such as pars reticulata of substantia nigra and globus pallidus. Finally, we will continue to assess the anatomical and pathological consequences of amphetamine and cocaine administration on the rat brain using tyrosine hydroxylase immunocytochemistry, the Fink-Heimer method for identifying degeneration in caudate nucleus and cerebral cortex, and biochemical analysis of potential monoamine depletions from these sites.
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1 |
| 1988 — 1997 |
Groves, Philip M |
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. |
Novel Modes of Actions of Abused Drugs @ University of California San Diego
Experiments are proposed to determine the mechanisms underlying alterations in catecholaminergic and non-catecholaminergic neuronal terminal excitability, including an analysis of the influence of cocaine on catecholaminergic terminal excitability and whether changes in terminal excitability of dopaminergic neurons in the rat brain occur in the chronically implanted, behaving animal. An attempt will be made to collect converging evidence regarding the identity and postsynaptic target of dopaminergic synapses made in neostriatum and to assess the relation of dopaminergic synapses made in neostriatum to its compartmentalization into the dopaminergic islandic or striosomal and matrix compartments. Further experiments are proposed to assess the consequences of amphetamine administration on neuronal activity in neostriatal targets such as pars reticulata of substantia nigra and globus pallidus. Finally, we will continue to assess the anatomical and pathological consequences of amphetamine and cocaine administration on the rat brain using tyrosine hydroxylase immunocytochemistry, the Fink-Heimer method for identifying degeneration in caudate nucleus and cerebral cortex, and biochemical analysis of potential monoamine depletions from these sites.
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| 1989 |
Groves, Philip M |
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. |
Training Program Basic Science Foundations of Psychiatry @ University of California San Diego |
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| 1997 — 1999 |
Groves, Philip M |
S06Activity Code Description:
To strengthen the biomedical research and research training capability of ethnic minority institutions, and thus establish a more favorable milieu for increasing the involvement of minority faculty and students in biomedical research. |
Basal Ganglia Anatomy and Physiology--Mechanisms of Action of Drugs of Abuse @ University of California San Diego
MBRS undergraduate students will participate in an on-going research program under the guidance of scientist-mentors. These studies on rodents will use electrophysiological, neuropharmacological, and anatomical approaches to reveal the actions of stimulant drugs in the caudate nucleus. This nucleus and its dopaminergic input from the substantia nigra are prominent sites for the action of stimulant drugs, including amphetamine and cocaine. In addition, this major integrative area of the basal ganglia is a significant locus for the pathology of Huntington's and Parkinson's disease. As well as elucidating the action of drugs of abuse, this research will reveal fundamental aspects of neuronal processing in the caudate nucleus and its associated afferent systems. Recent evidence suggests that presynaptic interactions occur in the caudate between dopaminergic nigrostriatal and glutamatergic corticostriatal afferents. These interactions appear to result from the activation of auto- and heteroreceptors located in afferent terminal regions by neurotransmitter released from nearby synapses. These presynaptic interactions may be an important locus for the action of stimulant drugs. Students will have the opportunity to participate in electrophysiological studies employing the measurement of terminal axon electrical excitability to investigate these interactions. Extracellular recording and the terminal excitability technique will also be used to examine possible alterations in both the firing properties of the dopaminergic neurons of the substantia nigra and changes in autoreceptor feedback regulation of the terminals of these neurons within the caudate nucleus related to the behavioral sensitization of the rats to amphetamine. We have previously observed that prenatal cocaine administration produces significant alterations in the rat caudate nucleus. Students will participate in structural studies employing correlated light and electron microscopic examination of basal ganglia and related regions. These experiments will use immunocytochemical techniques, image analysis, and computer assisted three-dimensional reconstruction to further elucidate the changes induced in the brains of these cocaine exposed animals. Anatomical studies are also proposed to accurately characterize the density of dopaminergic synapses, their postsynaptic sites, and the relation between these post-synaptic sites and those of other afferents to caudate neurons.
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| 1997 |
Groves, Philip M |
P41Activity Code Description:
Undocumented code - click on the grant title for more information. |
Char of Neostriatal Neurons Containing Aromatic L Amino Acid Decarboxylase @ University of California San Diego
technology /technique development; substance abuse related disorder; microscopy; biomedical resource; aging; Mammalia; nervous system; behavioral /social science research tag;
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| 1999 — 2001 |
Groves, Philip M |
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. |
Mechanism of Action of Drugs of Abuse--Amphetamine @ University of California San Diego
DESCRIPTION: (Adapted From The Applicant's Abstract) This application seeks renewal of research support to continue to study the sites and mechanisms of action of psychomotor stimulants. Its general aim is to study the effects of amphetamine on striatal glutamate and dopamine neurotransmission and the sites of termination of glutamate and dopamine axons relative to the different neostriatal output cells. Specifically, it will address three issues related to the effects of systemic amphetamine: the presynaptic mechanisms contributing to neostriatal changes associated with addiction, and the circuitry that brings about the amphetamine-induced increase in neuronal activity of the direct striatal output pathway. The motor effects of these drugs depend on their ability to increase dopamine (DA) transmission. Several motor responses are enhanced by repeated amphetamine administration; a phenomenon termed behavioral sensitization. Changes in the sensitivity of DA somatodendritic and terminal axon autoreceptors may contribute to behavioral sensitization. Experiments are proposed using terminal excitability, an in vivo electro- physiological measure of presynaptic receptor stimulation, and microdialysis to further study the bases for presynaptic changes in nigrostriatal DA axon terminals in sensitized rats. DA terminal fields in nucleus accumbens and prefrontal cortex will also be examined. Alterations in glutamatergic transmission may also be critical in the development of sensitization. Excitability measurements will assess possible presynaptic changes in the glutamatergic afferents to the neostriatum, nucleus accumbens and ventral tegmental area. Other studies will examine the relation between impulse-induced long-lasting changes in presynaptic corticostriatal excitability and postsynaptic expressions of long- term potentiation or depression. Electron microscopic studies are proposed to further elucidate the neostriatal circuitry involving the DA and glutamate afferent systems. It will be determined whether DA inputs onto spiny dendrites are associated with inputs from specific cortical and thalamic regions and if these patterns of convergence differ for spiny neurons identified as belonging to the direct and indirect output pathways. The thalamus is a major excitatory input to the striatum, yet little is known regarding differences in innervation from specific thalamic regions. Differences in the thalamic input onto cholinergic and spiny neurons participating in the two output pathways will be examined and the morphology and other afferents of these cells determined. The possibility of nonsynaptic release sites on nigrostriatal DA afferents will be assessed by labeling components of the release mechanism and then correlating them with the locations of dopamine receptors.
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