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.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Aging / genetics
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Aging / metabolism
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Aging / pathology
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Animals
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Brain / drug effects*
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Brain / metabolism
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Brain / physiopathology
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Cognition Disorders / drug therapy*
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Cognition Disorders / metabolism
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Cognition Disorders / physiopathology
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Indoles / pharmacology
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Indoles / therapeutic use
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Ki-67 Antigen / metabolism
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Male
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Memory Disorders / drug therapy*
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Memory Disorders / metabolism
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Memory Disorders / physiopathology
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Neuronal Plasticity / drug effects
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Neuronal Plasticity / physiology
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Piperazines / pharmacology
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Piperazines / therapeutic use
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Proliferating Cell Nuclear Antigen / metabolism
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RNA, Messenger / drug effects
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RNA, Messenger / metabolism
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Rats
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Rats, Inbred F344
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Rats, Long-Evans
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Receptor, Serotonin, 5-HT1A / drug effects
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Receptor, Serotonin, 5-HT1A / genetics
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Receptor, Serotonin, 5-HT1A / metabolism
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Receptor, Serotonin, 5-HT1B / drug effects
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Receptor, Serotonin, 5-HT1B / genetics
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Receptor, Serotonin, 5-HT1B / metabolism
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Receptors, Serotonin / drug effects*
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Receptors, Serotonin / genetics
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Receptors, Serotonin / metabolism
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Serotonin / metabolism*
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Serotonin Antagonists / pharmacology*
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Serotonin Antagonists / therapeutic use
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Tryptophan Hydroxylase / drug effects
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Tryptophan Hydroxylase / genetics
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Tryptophan Hydroxylase / metabolism
Substances
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Indoles
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Ki-67 Antigen
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Piperazines
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Proliferating Cell Nuclear Antigen
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RNA, Messenger
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Receptor, Serotonin, 5-HT1B
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Receptors, Serotonin
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Ro4368554
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Serotonin Antagonists
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serotonin 6 receptor
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Receptor, Serotonin, 5-HT1A
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Serotonin
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Tryptophan Hydroxylase
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tph2 protein, rat