This study examined the effects of chronic administration of the 5-HT6R antagonist, SB-258585, on cognitive, memory, and hippocampal plasticity in a rat model of AD.
Adult, male rats were divided into the following groups: control, sham, AD (saline treatment, 1 μL icv for 30 days), and AD + SB258585 (5-HT6R antagonist, 1 μg/μL icv for 30 days).
SUVN-502, a selective 5-HT6 receptor antagonist, was found to be active in preclinical models of cognitive deterioration suggesting a potential role in the treatment of dementia related to Alzheimer's disease.
Since 5-HT6 is almost exclusively expressed in the primary cilia, using immunostaining we examined the number of cilia in the hippocampus of AD animal model APP/PS1 mice.
Discovery of 5-HT6 receptor subtype and its exclusive localization within the central nervous system led to extensive investigations of its role in Alzheimer's disease, schizophrenia, and obesity.
Areas covered: This review discusses 5-HT6 antagonists currently in clinical trials as potential treatments for AD symptomatology and how 5-HT6 physiology may play a positive role in alleviating AD symptom pathophysiology.
In conclusion, the association of ApoE epsilon4 to AD in a sample of patients from the Basque Country is confirmed, though the association to C267T polymorphism of the 5-HT(6) receptor has not been observed.
Although there was a tendency toward an increased number of the genotype TT of the 5-HT6 receptor polymorphism in AD patients when compared to controls (2.8% vs. 1.3%), neither this nor the 5-HT2A promoter polymorphism showed significant differences in their genotypic or allelic distribution among patients and controls.
The difference in the 5-HT(6) genotype or allele distributions between the AD patients with depressive disorders (n = 25) and those without (n = 120) was not significant.