Effects of Apomorphine and L‐Methionine Sulphoximine on the Release of Excitatory Amino Acid Neurotransmitters and Glutamine in the Striatum of the Conscious Rat

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Abstract
The effects of apomorphine, a D1-, D2-dopamine receptor agonist, on the extracellular concentrations of excitatory amino acids, glutamic and aspartic acids, and on that of their precursor, glutamine, were investigated using an intracerebral perfusion system. Apomorphine produced a concentration-related rise in glutamic acid concentration in cerebral perfusates (P < 0.01) whereas only the highest concentration of apomorphine (3 x 10(-3) micrograms/microliters) increased the concentration of aspartic acid (P < 0.05). These effects were seen in the sample taken at the same time as the apomorphine injection. The rise in glutamine concentration (P < 0.01) produced by apomorphine continued for 10 min beyond perfusion with apomorphine. These effects were attenuated by previous injections of D1-, D2-dopamine receptor blocker. To investigate further the release of glutamine, the glutamine synthetase inhibitor L-methionine sulphoximine (MSO) was injected intracerebrally before apomorphine perfusion. After MSO pre-injection, the extracellular concentration of glutamine decreased (P < 0.01) to near zero concentrations. In MSO-treated animals, apomorphine did not induce the release of glutamic acid, aspartic acid or glutamine. These results indicate a role for dopamine in the release of excitatory amino acids and glutamine in the neostriatum of the rat. A possible volumetric interaction between dopamine and glutamic acid as well as the hypothesis of a striato-pallido-thalamo-cortico-striatal feedback loop are discussed.