Adenosine involvement in amitriptyline effect on glutamate and aspartate release in rat prefrontal cortex: K. Gołembiowska. Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smétna 12, PL 31–343 Kraków, Poland

Abstract

The spontaneous and depolarization-evoked release of radiolabeled d-aspartic acid, previously taken up by rat striatal slices, was studied by using a superfusion system. Veratridine (10–50 μM), electrical field stimulation (20 Hz, 1.0 V, 60 sec), and potassium (53 mM) markedly potentiated the release of d-[3H]aspartate from striatal slices. The release of l-[3H]glutamate was also increased by veratridine, according to a pattern and time course of release similar to that of d-[3H]aspartate. However, the ratio of d-[3H]aspartic acid release evoked by veratridine over spontaneous levels of release was much higher when compared to that of radiolabeled l-glutamate. Omission of calcium from the superfusion medium almost completely suppressed d-[3H]aspartate release evoked by veratridine or by electrical stimulation whereas high K+-evoked release of the [3H]amino acid was only slightly reduced. However, increasing Mg2+ concentration to 12 mM in the superfusion medium did substantially block d-[3H]aspartate release induced by K+-depolarization. Additional experiments showed that tetrodotoxin (1 μM), a blocker of voltage-dependent Na+ channels, totally abolished veratridine-evoked release of d-[3H]aspartate from striatal slices. Finally, lesion studies showed that unilateral ablation of the fronto-parietal cortex was accompanied by a significant decrease in the high-affinity uptake of striatal d-[3H]aspartate and by a large and parallel loss from striatal slices in d-[3H]aspartate release evoked by either veratridine or high K+. In contrast, unilateral injection of kainic acid into the striatum did not influence depolarization-evoked release of d-[3H]aspartate from striatal slices. The findings reported suggest that d-[3H]aspartic acid may be taken up preferentially and then released, in a Ca2+-dependent manner, by veratridine and electrical stimulation from nerve terminals belonging to the cortico-striatal pathway. In addition, the results provide further support for the view that excitatory amino acids may act as neurotransmitters at the cortico-striatal nerve fibers.