A number of animal models of human epilepsy have been developed and are used in attempts to determine the neurophysiological and neurochemical basis of the human disease. We believe that our model, the genetically derived epilepsy-prone rat, can serve as an excellent model for study of the neurochemical basis of epilepsy (see Appendix A for relevant reviews). These animals represent a unique and valuable resource. They are not commercially available and there are only three existing colonies. One is our own and it is maintained in Shreveport, LA in our facilities. The second is housed at the University of Arizona, while the third is housed at the University of Moscow. The present proposal is designed to provide a detailed neurochemical evaluation of monoaminergic neuronal tracts in the central nervous system of this model. The evaluation will be carried out in an attempt to correlate sound-induced seizure susceptibility and intensity with neurochemical abnormalities. Epilepsy-prone animals and control animals will be obtained from the Principal Investigator's colonies. In initial studies, six areas of the central nervous system will be evaluated. These are: the spinal cord, pons-medulla, cerebellum, midbrain, hypothalamus-thalamus and telencephalon. Any differences found in these large areas will be traced to more specific structures by further dissection. In these structures, we intend to estimate the functional integrity of noradrenergic, serotonergic and dopaminergic nerve tracts by measuring: (1) neurotransmitter turnover; (2) activities of enzymes involved in synthesis of the amines; and (3) tissue levels of neurotransmitter metabolites.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
7R01NS022672-01
Application #
3405394
Study Section
Neurology A Study Section (NEUA)
Project Start
1985-01-01
Project End
1986-06-30
Budget Start
1985-01-01
Budget End
1986-06-30
Support Year
1
Fiscal Year
1985
Total Cost
Indirect Cost
Name
College of Medicine at Peoria
Department
Type
Schools of Medicine
DUNS #
City
Peoria
State
IL
Country
United States
Zip Code
61605
Clough, R W; Browning, R A; Maring, M L et al. (1994) Effects of intraventricular locus coeruleus transplants on seizure severity in genetically epilepsy-prone rats following depletion of brain norepinephrine. J Neural Transplant Plast 5:65-79
Wang, C; Mishra, P K; Dailey, J W et al. (1994) Noradrenergic terminal fields as determinants of seizure predisposition in GEPR-3s: a neuroanatomic assessment with intracerebral microinjections of 6-hydroxydopamine. Epilepsy Res 18:1-9
Jobe, P C; Mishra, P K; Browning, R A et al. (1994) Noradrenergic abnormalities in the genetically epilepsy-prone rat. Brain Res Bull 35:493-504
Mishra, P K; Burger, R L; Bettendorf, A F et al. (1994) Role of norepinephrine in forebrain and brainstem seizures: chemical lesioning of locus ceruleus with DSP4. Exp Neurol 125:58-64
Yan, Q S; Jobe, P C; Dailey, J W (1993) Thalamic deficiency in norepinephrine release detected via intracerebral microdialysis: a synaptic determinant of seizure predisposition in the genetically epilepsy-prone rat. Epilepsy Res 14:229-36
Mishra, P K; Kahle, E H; Bettendorf, A F et al. (1993) Anticonvulsant effects of intracerebroventricularly administered norepinephrine are potentiated in the presence of monoamine oxidase inhibition in severe seizure genetically epilepsy-prone rats (GEPR-9s). Life Sci 52:1435-41
Yan, Q S; Jobe, P C; Dailey, J W (1993) Noradrenergic mechanisms for the anticonvulsant effects of desipramine and yohimbine in genetically epilepsy-prone rats: studies with microdialysis. Brain Res 610:24-31
Ludvig, N; Mishra, P K; Yan, Q S et al. (1992) The paradoxical effect of NMDA receptor stimulation on electrical activity of the sensorimotor cortex in freely behaving rats: analysis by combined EEG-intracerebral microdialysis. Synapse 12:87-98
Dailey, J W; Yan, Q S; Mishra, P K et al. (1992) Effects of fluoxetine on convulsions and on brain serotonin as detected by microdialysis in genetically epilepsy-prone rats. J Pharmacol Exp Ther 260:533-40
Ludvig, N; Mishra, P K; Yan, Q S et al. (1992) The combined EEG-intracerebral microdialysis technique: a new tool for neuropharmacological studies on freely behaving animals. J Neurosci Methods 43:129-37

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