The behavior and neurotransmitter contents in brain structures of rats with Alzheimer’s disease modeled by administration of Aβ25–35

Abstract

We studied behavioral and neurochemical alterations that were induced by modeling of Alzheimer’s disease (AD) using bilateral intracerebroventricular administration of Aβ25–35 at a dose of 7.5 nmol in each ventricle. After 5.5 weeks, cognitive and psychoemotional alterations in the Morris spatial learning and Porsolt’s forced-swim tests were observed in rats with strong symptoms that are typical of AD. Measurement of the contents of monoamines and their metabolites in rat-brain structures was performed using the HPLC with the ECD method 1 day after the end of the tests. In the dorsal striatum, we found a decrease in the contents of metabolites of dopamine (DA), including homovanillic acid (HVA), 3,4-dihydroxyphenylacetic acid (DOPAC), and 3-methyltyramine (3-MT), and a decrease in the indices of DA utilization, including DOPAC/DA and HVA/DA, whereas the DA content was stable in this structure. In the nucleus accumbens (NA, ventral striatum), we found a decreased level of the HVA/DA ratio, which reflects the lower turnover of extracellular DA. We also found a lower turnover of serotonin (5-HT), which was seen as a decrease in the 5-hydroxyindolacetic acid (5-HIAA)/5-HT ratio, whereas the 5-HT content was elevated. In the hypothalamus, we revealed a significant decrease in the DA level and the levels of its metabolites, including 3-MT and HVA, and 5-HT turnover. We found that Aβ25–35 influenced the indices of amino-acidergic neurotransmission, which was reflected by the higher glutamate content in the striatum. Our data show that cerebral neurotransmitter systems, such as the tuberoinfundibular, mesolimbic, and nigrostrial dopaminergic and the striatal serotonergic and glutamatergic systems, are involved in pathophysiological mechanisms of the development of cognitive and psychoemotional impairments that occur in AD, as modeled by administration of Aβ25–35.