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.(ABSTRACT TRUNCATED AT 250 WORDS)