Dopamine D-1 regulation of caudate neurotensin mRNA in the presence or absence of the nigrostriatal dopamine pathway

Changes in extrapyramidal dopamine (DA) function significantly alter the ac tivity of striatal neurotensin (NT) systems. Specifically, stimulation of D A D-l or D-2 receptors increases or decreases striatal NT tissue levels, re spectively. In contrast, removal of D-2 receptor basal activity with either an antagonist or lesion of the nigrostriatal DA projection increases stria tal NT content. To understand better the significance of these changes in t he levels of NT peptide, we determined the effects of treatment with the se lective D-l agonist, SKF 82958, alone or in combination with a lesion of th e nigrostriatal DA pathway, on the levels of NT mRNA in various regions of the caudate nucleus. Removal of at least 90% of this DA pathway significant ly increased NT mRNA in most, but not all, regions throughout the caudate n ucleus. In contrast, four, but not one, administrations of SKF 82958 (2 mg kg(-1) dose(-1)) increased NT mRNA levels in principally middle, but not ro stral, caudate regions. Lesioning the nigrostriatal DA pathway enhanced the effects of SKF 82958 so that a lower, single dose (1 mg/kg) of this D-l ag onist also increased NT mRNA levels predominantly in the middle caudate sec tions. These findings demonstrate that DA D-l receptors profoundly regulate the striatal expression of NT mRNA in a regionally selective fashion, whic h appears to be unique from that principally influenced by DA D-2 regulatio n. (C) 1999 Elsevier Science B.V. All rights reserved.