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 dizocilpine maleate alone or in combination with unilateral 6-hydroxydopamine-induced lesion of the nigrostriatal dopaminergic neurons on the number and staining intensity of neuropeptide Y-immunoreactive neurons in the rat striatum. In the combined condition, short-term and long-term treatments with dizocilpine maleate were started 19 days and 12 days after the lesion of the nigrostriatal dopaminergic pathway, respectively. As reported previously, the unilateral dopaminergic lesion elicited an increase in both the number and staining intensity of neuropeptide Y-immunoreactive neurons in the ipsilateral striatum. Short-term treatment 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 not modify neuropeptide Y immunostaining, totally suppressed the effect of the dopaminergic deafferentation on the number of neuropeptide Y-positive 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 mg/kg, dizocilpine maleate by itself elicited an increase in the number of neuropeptide Y-immunodetectable cells, paradoxically concomitant with a decrease in the levels of intraneuronal labelling. After combination of this treatment with unilateral lesion of the nigrostriatal dopaminergic pathway, the changes related to either the dizocilpine maleate treatment or the 6-hydroxydopamine-induced lesion totally disappeared, so that the number and staining intensity of neuropeptide Y-immunoreactive neurons in that condition did not differ from control values. Taken altogether, these data indicate that neuronal neuropeptide Y levels in the striatum undergo tonic excitatory amino acid influence through N-methyl-D-aspartate receptors, and further suggest that reciprocal interactions between the dopaminergic and glutamatergic afferent systems are involved in the regulation of striatal neuropeptide Y metabolism. The present data also provide evidence that some postsynaptic effects of the nigrostriatal dopaminergic deafferentation on striatal neurons may be mediated via mechanisms involving excitatory amino acid receptors of the N-methyl-D-aspartate subtype.