Regulation of the concentration of dynorphin A1-8 in the striatonigral pathway by the dopaminergic system

Abstract

The purpose of this study was to explore the dopaminergic control of the striatonigral dynorphin system by measuring the levels of dynorphin A1-8-like immunoreactivity (DN-LI) after repeated injections of a dopaminergic receptor agonist or antagonist. Seven daily injections of different doses of apomorphine (0.5, 1.0, 2.5 and 5.0 mg/kg, s.c.) caused a significant dose-related increase of DN-LI in the striatum (26, 34, 63, 85% over control at each corresponding dose). Similar increases were observed in the substantia nigra (22, 52, 50 and 62% over control). In another experiment, rats received 5 mg/kg of apomorphine for 1, 3, and 7 days. There was a significant time-related increase in DN-LI both in the striatum (37, 50 and 85% over control at each corresponding period) and in the substantial nigra (32, 78 and 62%). Repeated administration of haloperidol (1 mg/kg, i.p.) failed to change the striatal level of DN-LI, but, when given at the same time as apomorphine, significantly attenuated the effect of apomorphine. These results suggest that dopamine exerts a modulatory influence on the metabolism of dynorphin in the striatonigral pathway.