β-Amyloid and Lithium Affect the Magnitude of Phasic Dopamine Release in the Shell of the Nucleus Accumbens

Abstract

Published data indicate that impairments to dopaminergic secretion in the shell of the nucleus accumbens play a role in the pathogenesis of Alzheimer’s disease (ad). The likely cause is an increase in the toxic form of β-amyloid in the brain. Like other pathogenetic processes in AD, this impairment may be mediated by an increase in glycogen synthase kinase 3 (GSK3) activity. The aim of the present work was to study the effect of β-amyloid on dopamine release in the shell of the nucleus accumbens. Changes in the dopamine level in the shell of the nucleus accumbens were recorded in vivo in 38 anesthetized male Wistar rats by fast scan cyclic voltammetry before and 1.5 h after experimental treatment. The ability of dopaminergic neurons to secrete dopamine was assessed in terms of the amplitude of responses to electrical stimulation of the ventral tegmental area (VTA). Neurotoxic processes typical of AD were modeled by giving β-amyloid (fragment 25–35) solution into the ventricular system of the brain. The role of GSK34 in mediating the effects of β-amyloid were evaluated by blocking the activity of this enzyme with an inhibitor, i.e., lithium. Lithium chloride solution at the “therapeutic” dose of 10.4 mg/kg was given i.p. immediately after β-amyloid injections. Increases in stimulated dopamine release provided evidence that during the 1.5 h after administration of both β-amyloid and lithium, the ability of ventral tegmental area neurons to secret dopamine in the shell of the nucleus accumbens was increased. Furthermore, comparison with the control group showed that these substances countered weakening of the secretory function induced by the experimental conditions. Lithium given simultaneously with β-amyloid weakened its action, evidencing involvement of GSK3 in this process.