Soluble amyloid beta(1-42) reduces dopamine levels in rat prefrontal cortex: relationship to nitric oxide.

Several studies suggest a pivotal role of amyloid beta (Ab)1-42 and nitric oxide (NO) in the pathogenesis of Alzheimer’s disease. NO also possess central neuromodulatory properties. To study the soluble Ab1-42 effects on dopamine concentrations in rat prefrontal cortex, microdialysis technique was used. We showed that i.c.v. injection or retrodialysis Ab1-42 administration reduced basal and K-stimulated dopamine levels, measured 2 and 48 h after peptide administration. Immunofluorescent experiments revealed that after 48 h from i.c.v. injection Ab1-42 was no longer detectable in the ventricular space. We then evaluated the role of NO on Ab1-42-induced reduction in dopamine concentrations. Subchronic L-arginine administration decreased basal dopamine levels, measured either 2 h after i.c.v. Ab1-42 or on day 2 post-injection, whereas subchronic 7-nitroindazole administration increased basal dopamine concentrations, measured 2 h after i.c.v. Ab1-42 injection, and decreased them when measured on day 2 post-Ab1-42-injection. No dopaminergic response activity was observed after K stimulation in all groups. These results suggest that the dopaminergic system seems to be acutely vulnerable to soluble Ab1-42 effects. Finally, the opposite role of NO occurring at different phases might be regarded as a possible link between Ab1-42-induced effects and dopaminergic dysfunction.