This research is of a twofold nature--to study both the static and dynamic properties of the biogenic monoamines. Detailed three-dimensional maps of the concentrations of norepinephrine (NE), dopamine (DA), 5-hydroxytryptamine (5-HT) and ascorbic acid (AA) in thalamus, frontal cortex and cingulate cortex will be developed by gridding coronal slices of brain tissue and analyzing each section by high performance liquid chromatography with electrochemical detection. Special emphasis will be placed on studying the DA distributions, since this has already shown surprising variability in rat thalamus. The possibility that this excessive variability among animals extends to rat frontal cortex will be especially examined. The unusual variability of DA innervation has significant implications in the current biological theories of schizophrenia. The technique of in vivo voltammetry will be used to measure the release of NE in rat thalamus elicited by peripheral somatosensory stimulation. While it is widely believed that NE is released and may modulate incoming sensory information in cortex and other brain regions, no proof of its in vivo release has been forthcoming. The use of a newly developed measurement which combines in vivo voltammetry (to measure biogenic amine release) and ion-selective micropipets (to measure extracellular fluxes of ions) will be applied to studying sensory processing in the rat thalamus. Some recently developed micro chemical probes will be used to develop rapid, sensitive sampling techniques for brain tissue which should be amenable to automation. Such systems could have widespread use in both brain and chemical assays.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS008740-26
Application #
3393811
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1976-09-20
Project End
1993-05-31
Budget Start
1991-12-01
Budget End
1993-05-31
Support Year
26
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Kansas Lawrence
Department
Type
Schools of Arts and Sciences
DUNS #
072933393
City
Lawrence
State
KS
Country
United States
Zip Code
66045
Mitchell, K; Oke, A F; Adams, R N (1994) In vivo dynamics of norepinephrine release-reuptake in multiple terminal field regions of rat brain. J Neurochem 63:917-26
Capella, P; Ghasemzadeh, M B; Adams, R N et al. (1993) Real-time monitoring of electrically stimulated norepinephrine release in rat thalamus: II. Modeling of release and reuptake characteristics of stimulated norepinephrine overflow. J Neurochem 60:449-53
Ghasemzadeh, M B; Capella, P; Mitchell, K et al. (1993) Real-time monitoring of electrically stimulated norepinephrine release in rat thalamus: I. Resolution of transmitter and metabolite signal components. J Neurochem 60:442-8
Mitchell, K; Adams, R N (1993) Comparison of the effects of voltage-sensitive calcium channel antagonism on the electrically stimulated release of dopamine and norepinephrine in vivo. Brain Res 604:349-53
Cammack, J; Ghasemzadeh, B; Adams, R N (1992) Electrochemical monitoring of brain ascorbic acid changes associated with hypoxia, spreading depression, and seizure activity. Neurochem Res 17:23-7
Oke, A F; Putz, C; Adams, R N et al. (1992) Neuroleptic treatment is an unlikely cause of elevated dopamine in thalamus of schizophrenic subjects. Psychiatry Res 45:203-8
Renner, K J; Pazos, L; Adams, R N (1992) In vivo voltammetric evidence for the detection of norepinephrine release in the thalamus of freely moving rats. Brain Res 577:49-56
Ghasemzadeh, B; Cammack, J; Adams, R N et al. (1991) Dynamic changes in extracellular fluid ascorbic acid monitored by in vivo electrochemistry. Brain Res 547:162-6
Cammack, J; Oke, A; Adams, R N (1991) Simultaneous high-performance liquid chromatographic determination of ascorbic acid and dehydroascorbic acid in biological samples. J Chromatogr 565:529-32
Cammack, J; Ghasemzadeh, B; Adams, R N (1991) The pharmacological profile of glutamate-evoked ascorbic acid efflux measured by in vivo electrochemistry. Brain Res 565:17-22

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