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Malfunction of the serotonin system may contribute to memory deficits during aging. We evaluated the 5-HT(6) antagonist RO4368554 in two models of learning and memory in aged rats. Male rats (18 months) were assigned to two groups of equal cognitive performance. After 2 weeks of 5-HT(6) antagonist RO4368554 (5 mg/kg, i.p.) treatment, rats showed significant improvement in object recognition and social discrimination compared with rats given chronic vehicle. Brains from these animals were examined for changes in plasticity-associated proteins Ki-67 and PCNA. No differences were seen between groups in any of these markers. We also measured mRNA expression of 5-HT(6), along with 5-HT(1A), 5-HT(1B), and tryptophan hydroxylase-2 mRNAs in 4-month-old and 24-month-old F344 rats. Decreases in 5-HT(1B) expression were observed in several forebrain regions in the old rats. These results demonstrate that 5-HT(6) and 5-HT(1B) receptors are potential targets for treatment of age-related memory disorders.
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Mitchell et al. (2009) studied this question.
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