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.
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