Action and Interaction of Amyloid-β and Insulin on the Dopamine Release and Reuptake in the Lateral Dorsal Striatum of Rats

Abstract

Abstract Accumulation of amyloid-β (Aβ) in the brain is an important link in the pathogenesis of Alzheimer's disease. Experimental studies show that Aβ can cause the dopaminergic dysfunction that is characteristic of this disease, and under Aβ influence not only the decrease but also the increase in phasic dopamine release is possible, depending on the structure of the brain. We aimed to investigate whether Aβ in a toxic form affects dopamine release or reuptake in the lateral dorsal striatum and, if so, whether this influence is mediated by the insulin signaling pathway. Aβ (fragment 25-35) and insulin solution were injected into the ventricular system of the anesthetized male Wistar rats. Within 10 minutes before and 30 minutes after the injection, electrically evoked dopamine elevations were registered with fast-scan cyclic voltammetry every 5 minutes. Release and reuptake were assessed separately by the kinetic analysis. The results show that Aβ acts on dopamine release and reuptake in the lateral dorsal striatum in several ways. It modulates the effect of insulin on dopamine release and reuptake, apparently acting through the insulin signaling pathway. In addition, Aβ increases dopamine release and basal levels by acting aside of the insulin signaling pathway.