REVERSAL OF THE ADAPTIVE RESPONSE OF NEUROPEPTIDE-Y NEURONS IN THE RAT STRIATUM TO NIGROSTRIATAL DOPAMINE DEAFFERENTATION BY THE N-METHYL-D-ASPARTATE ANTAGONIST DIZOCILPINE MALEATE

This study examined the effects of systemic treatments with dizocilpin e maleate alone or in combination with unilateral 6-hydroxydopamine-in duced lesion of the nigrostriatal dopaminergic neurons on the number a nd staining intensity of neuropeptide Y-immunoreactive neurons in the rat striatum. In the combined condition, short-term and long-term trea tments with dizocilpine maleate were started 19 days and 12 days after the lesion of the nigrostriatal dopaminergic pathway, respectively. A s reported previously, the unilateral dopaminergic lesion elicited an increase in both the number and staining intensity of neuropeptide Y-i mmunoreactive neurons in the ipsilateral striatum. Short-term treatmen t with dizocilpine maleate at the dose of 0.2 mg/kg (four injections, 6 h apart, sacrifice 2 h after the final dose), which by itself did no t modify neuropeptide Y immunostaining, totally suppressed the effect of the dopaminergic deafferentation on the number of neuropeptide Y-po sitive neurons but not that on the intraneuronal amount of labelling. When administered twice a day for eight days at the same dose of 0.2 m g/kg, dizocilpine maleate by itself elicited an increase in the number of neuropeptide Y-immunodetectable cells, paradoxically concomitant w ith a decrease in the levels of intraneuronal labelling. After combina tion of this treatment with unilateral lesion of the nigrostriatal dop aminergic pathway, the changes related to either the dizocilpine malea te treatment or the 6-hydroxydopamine-induced lesion totally disappear ed, so that the number and staining intensity of neuropeptide Y-immuno reactive neurons in that condition did not differ from control values. Taken altogether, these data indicate that neuronal neuropeptide Y le vels in the striatum undergo tonic excitatory amino acid influence thr ough N-methyl-D-aspartate receptors, and further suggest that reciproc al interactions between the dopaminergic and glutamatergic afferent sy stems are involved in the regulation of striatal neuropeptide Y metabo lism. The present data also provide evidence that some postsynaptic ef fects of the nigrostriatal dopaminergic deafferentation on striatal ne urons may be mediated via mechanisms involving excitatory amino acid r eceptors of the N-methyl-D-aspartate subtype.