Amino acids in rat neostriatum: alteration by kainic acid lesion.

Unilateral stereotaxic injection of 10 nmol of the glutamomimetic substance, kainic acid, into the rat striatum caused permanent, significant decreases in the levels of glutamate (40--50%), aspartate (35--40%), taurine (20--30%) and GABA (60--70%). There were initial, transient decreases in serine, glycine and alanine which returned to normal values within 16--32 days after injection. Glutamine levels were not altered in lesioned striatum. This coincided with a 55% increase in glutamine synthetase activity in the lesioned striatum compared either to the non-injected striatum or controls injected with saline. The high affinity uptake of choline by synaptosomal preparations of lesioned striatum was decreased by 70% compared to controls whereas that of glutamate/aspartate was either unchanged or somewhat on a per mg protein basis. This latter point may be illusory in that, because of widespread neuronal destruction, the total 'synaptosomal' protein obtained from the lesioned striata was only about 50% that from control tissue. The biochemical data are consistent with the histological and behavioral effects of kainic acid administration. The unchaning glutamine levels and increase in glutamine synthetase activity are consistent with the widespread gliosis and the lack of change in glutamate/aspartate high affinity uptake is consistent with a sparing of afferent terminals. The large decrease in glutamate and aspartate is consistent with hypotheses concerning the intraneuronal localization of a major pool of these amino acids, especially in GABAergic neurons. The decrease in taurine suggests that a portion of this amino acid in striatum is probably associated with neurons destroyed by kainic acid. The bulk of the taurine, however, is therefore associated either with glial cells or the afferents to the striatum.