Regulation of the metabolism of striatal dynorphin by the dopaminergic system

Abstract

The purpose of this study was to explore the dopaminergic control of the striatonigral dynorphin system. Seven daily injections of a dopamine (DA) agonist, apomorphine (APO, 5 mg/kg, b.i.d., s.c.), caused a significant increase of dynorphin A (1-8)-like immunoreactivity (DN-LI) in the striatum (140% over control) and substantia nigra (41% over control) without changing DN-LI in frontal cortex, hypothalamus and hippocampus. Immunocytochemistry revealed intense dynorphin A (1-17)-like immunostaining in striatal "patch" neurons and striatonigral fibers after APO treatment. In order to understand the mechanism of increase in the peptide level, the abundance of preprodynorphin mRNA was quantified by Northern blot hybridization with a 32P-labeled cRNA probe coding for rat preprodynorphin. Seven daily injections of APO increased the abundance of striatal preprodynorphin mRNA by 60%. In another experiment, rats received a single injection of various doses of APO (0.5-2.5 mg/kg s.c.). Striatal DN-LI was decreased by 15% 1 hr after injection of a dose of 2.5 mg/kg of APO. Seven daily injections or a single injection of D-amphetamine produced effects similar to those elicited by APO. These studies reveal that the nigrostriatal DA system plays an important role in modulating the metabolism of striatonigral dynorphin-containing neurons.