Motor effects following application of putative excitatory amino acid antagonists to the region of the mesencephalic dopamine cell bodies in the rat.

The excitatory amino acid antagonists 2-amino-5-phosphonovalerate and gamma-D-glutamylglycine have been applied focally to the ventral tegmental area and both the pars compacta and pars reticulata of the substantia nigra of the rat. The injections were performed under halothane anaesthesia so that behavioural effects could be observed 5 min afterwards. Bilateral application of either antagonist to the ventral tegmental area and the pars compacta of the substantia nigra induced enhanced locomotor activity in an open field. This effect was blocked by pretreatment of the animals with a low dose of the dopamine receptor antagonist fluphenazine. Bilateral application of either antagonist to the pars reticulata of the substantia nigra produced sedation and a reduction in locomotor activity. Unilateral injection of either of the excitatory amino acid antagonists into the pars reticulata or pars compacta of the substantia nigra both resulted in contraversive circling behaviour. The effect of intranigral (both pars compacta and reticulata) 2-APV and gamma-DGG was accompanied by a significant increase in concentrations of both 3,4-dihydroxyphenylacetic acid (to 158-160% of control following injection into pars compacta, and 134-146% of control injected into pars reticulata) and homovanillic acid (to 161-166% of control following injection into pars compacta, and 186-210% of control injected into pars reticulata) in the ipsilateral striatum. Pretreatment of these animals with fluphenazine (0.3 mg/kg) antagonized this circling behaviour. These results indicate that antagonism of excitatory amino acid receptors in the region of the midbrain of the rat leads to specific behavioural effects which may in part be mediated through the ascending dopaminergic projections.