Dopamine-glutamate interactions in the prefrontal cortex of the conscious rat: studies on ageing

The effects of apomorphine, a D1-D2 dopamine receptor agonist, on the extracellular concentration of glutamate were investigated in the medial prefrontal cortex of young, middle-aged and aged rats. In vivo intracerebral perfusions were undertaken in the conscious rat using a concentric push-pull cannula system. Glutamate concentration in the samples were determined by HPLC with fluorometric detection. Apomorphine produced an increase in extracellular concentration of glutamate in medial prefrontal cortex of young rats (178% of baseline) only at 10 microM, but not at 5 and 20 microM. This increase in glutamate concentration induced by apomorphine was significantly attenuated by blockade of D1-D2 dopamine receptors with haloperidol. Apomorphine, at 10 microM, failed to induce an increase in extracellular concentration of glutamate in the prefrontal cortex of middle-aged and aged rats. However, at 20 microM, apomorphine induced an increase in glutamate concentration in the prefrontal cortex of middle-aged rats, but not in aged rats. These data indicate that an interaction between dopamine and glutamate exists in the medial prefrontal cortex and that this interaction deteriorates with age.