Journal
BRAIN RESEARCH
Volume 1008, Issue 1, Pages 40-48Publisher
ELSEVIER
DOI: 10.1016/j.brainres.2004.02.025
Keywords
serotonin; circadian rhythm; 8-OH-DPAT
Categories
Funding
- NIA NIH HHS [AG 13418] Funding Source: Medline
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Aging leads to many changes in the circadian timekeeping system, including reduced sensitivity to phase-resetting signals such as systemic administration of the serotonergic agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). In previous studies, we observed an age-related decrease in 5-HT7 receptor binding sites, one of the receptor subtypes that is activated by 8-OH-DPAT, in the dorsal raphe nucleus. In this Study, we tested the hypotheses that (I) aging reduces circadian phase shifts induced by local administration of 8-OH-DPAT (30 muM, i.e., 1.97 ng) or 5-carboxamidotryptamine (5-CT, 100 nM, i.e., 6.39 pg), another serotonin against, into the dorsal raphe and (2) 5-HT7 receptors mediate the phase shifts induced by administration of 5-CT and 8-OH-DPAT into the dorsal raphe. Young (3-5 months), middle-aged (12-13 months) and old hamsters (17-19 months) Were Surgically implanted with chronic guide cannulae aimed at the dorsal raphe, and were housed in cages equipped with running wheels. Aging significantly inhibited ( P<0.01) the phase advances in running-wheel rhythms induced by 8-OH-DPAT microinjected during the midsubjective day. 5-CT induced phase advances tended to decrease with aging, but this effect was not significant (P<0.12). Microinjection of the selective 5-HT7 receptor antagonist, SB-269970-A (50-5000 nM, i.e., 0.39-390 pg), 15 min before microinjection of 5-CT or 8-OH-DPAT into the dorsal raphe young hamsters, significantly inhibited phase shifts. In conjunction with our previous study, these findings indicate that an age-related reduction in 5-HT7 receptors in the dorsal raphe nucleus is ail important neurochemical mechanism leading to aging deficits in the cireadian timekeeping system. (C) 2004 Elsevier B.V. All rights reserved.
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