Soluble amyloid beta1-42 reduces dopamine levels in rat prefrontal cortex: relationship to nitric oxide.

Several studies suggest a pivotal role of amyloid beta (Aβ)1-42 and nitric oxide (NO) in the pathogenesis of Alzheimer’s disease. NO also possess central neuromodulatory properties. To study the soluble Aβ1-42 effects on dopamine concentrations in rat prefrontal cortex, microdialysis technique was used. We showed that i.c.v. injection or retrodialysis Aβ1-42 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 Aβ1-42 was no longer detectable in the ventricular space. We then evaluated the role of NO on Aβ1-42-induced reduction in dopamine concentrations. Subchronic l-arginine administration decreased basal dopamine levels, measured either 2 h after i.c.v. Aβ1-42 or on day 2 post-injection, whereas subchronic 7-nitroindazole administration increased basal dopamine concentrations, measured 2 h after i.c.v. Aβ1-42 injection, and decreased them when measured on day 2 post-Aβ1-42-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 Aβ1-42 effects. Finally, the opposite role of NO occurring at different phases might be regarded as a possible link between Aβ1-42-induced effects and dopaminergic dysfunction.