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Adaptations in 5-HT Receptor Expression and Function: Implications for Treatment of Cognitive Impairment in Aging

Ellen S Mitchell, Ross A McDevitt, John F Neumaier

J Neurosci Res. 2009 Sep;87(12):2803-11.

PMID: 19396878

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP478082994 Ro4368554 Ro4368554 478082-99-4 Price
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