EFFECTS OF AMYLOID- AND LITHIUM ON THE PHASIC DOPAMINE RELEASE IN THE NUCLEUS ACCUMBENS SHELL

According to the literature, impairment of dopaminergic secretion in the nucleus accumbens shell (NAc shell) can be caused by elevated level of amyloid beta in the brain, and this may be relevant in the pathogenesis of Alzheimer's disease (AD). As for the other manifestations of AD, this disturbance can be mediated by enhancement of activity of glycogen synthase kinase 3 (GSK3). This study aims to investigate influence of the increase of the amyloid beta level in the rat brain on the secretory activity of the dopaminergic neurons in the NAc shell. Changes of dopamine level in the NAc shell were measured in vivo in 38 anesthetized male Wistar rats with fast-scan cyclic voltammetry. Capacity of dopaminergic neurons to dopamine secretion was assessed by amplitude of dopamine level elevation due to electrical stimulation of the ventral tegmental area (VTA). To simulate neurotoxic processes specific to AD, a solution of amyloid p (fragment 25-35) was injected into the ventricular system of the rat brain. The role of GSK3 in amyloid beta effects was evaluated by blocking the activity of this enzyme using lithium as an inhibitor. 0.15 M solution of lithium chloride in a "therapeutic" dose of 1.63 ml/kg (10.4 mg/kg) was administered intraperitoneally immediately after the injection of amyloid-P. Increase of evoked dopamine release indicated that within one and a half hours after administration of beta-amyloid or lithium, the ability of neurons of the VTA to secrete dopamine into the NAc shell was enhanced. Moreover, a comparison with the control group showed that these substances eliminate the decrease of the secretory function caused by the experimental conditions. However, while administered together, beta-amyloid and lithium reduced the effects of each other.