Taurine (2-aminoethane sulfonic acid) is one of the most abundant inhibitory amino acids in the mammalian central nervous system (CNS). Substantial evidence exists to suggest that this amino acid is a physiological modulator of neuronal excitability. Taurine is also a potent anticonvulsant in a variety of animal epilepsies and in certain human epileptics. The mechanisms of these neuromodulatory and anticonvulsant actions of taurine are not known. I have investigated a proposed relationship between altered amino acid metabolism, seizure-susceptibility and the anticonvulsant action of taurine. The findings of the work presented in this dissertation indicate that in the genetically seizure-susceptible rat there are alterations in the subcellular concentration and transport of taurine. Furthermore, the data presented here indicate that these alterations in the CNS handling of taurine are not a consequence of seizure activity but rather may be contributing to the seizure-susceptibility. This supports the hypothesis that taurine is a physiological modulator of neuronal excitability and that defects in this neuromodulatory process may contribute to seizure-susceptibility. The action of taurine was found to not be mediated by a redistribution of glutamate in the brain but instead may be by increasing the conversion of glutamate to GABA.

Removal of the pineal gland from partially parathyroidectomized rats produces stereotyped violent seizures. Inasmuch as the neurotransmitter norepinephrine (NE) has been implicated in this experimental paradigm, the purpose of this study was to investigate the effect of specific alterations in catecholamine function on convulsions produced by pinealectomy (PinX). Additionally, the role of various pineal substances, sex differences and the caging paradigm in the convulsive response was studied. Male and female rats (grouped five per cage) were found to respond similarly to the convulsive stimulus of parathyroidectomy followed by PinX. Neither implants of melatonin nor ventricular injections of arginine vasotocin in isolated and grouped rats, respectively, produced consistent changes in convulsions from PinX. The method of caging the rats after PinX, however, dramatically influenced seizures. Isolated rats (one per cage) convulsed significantly later after PinX and did so less often than grouped (five per cage) controls. NE neurotransmission appears to play a strong role in influencing PinX-induced seizures. Augmenting NE function with desipramine suppressed seizures. Convulsions were enhanced by the (beta)-receptor antagonist timolol, while neonatal injections of the catecholamine neurotoxin 6-OHDA potentiated seizures so markedly that many rats died from just one convulsion. NE levels were significantly reduced in the telencephalons and increased in the brain stems of sham-pinealectomized rats which had also received neonatal 6-OHDA; telencephalic levels of DA were elevated by 6-OHDA. Both the proconvulsant effects of 6-OHDA and the alterations it produced in central catecholamine levels were prevented, for the most part, by pretreatment with DMI. Altering both NE and DA function with L-dihydroxyphenylalanine, (alpha)-methyl-p-tyrosine, FLA-63 or reserpine did not significantly affect PinX-induced seizures in isolated rats. NE appears to play a strong role in modulating PinX-induced seizures; however, a deficit in NE function per se does not seem to be the fundamental cause of the seizures since sham-pinealectomized rats having lowered NE and/or DA function did not convulse.