Age-related decline in striatal dopamine release and motoric function in Brown Norway/Fischer 344 hybrid rats

David M. Yurek, Susan B. Hipkens, Meleik A. Hebert, Don M. Gash, Greg A. Gerhardt

Research output: Contribution to journalArticlepeer-review

79 Scopus citations

Abstract

The Brown Norway/Fischer 344 F1 hybrid rats (F344BNF1) is a newer rat model and is emerging as an important rodent model of aging. In the present study we used motoric performance tests, intracerebral microdialysis, and neurochemical measures of postmortem brain tissue to investigate the effects of aging in young (4-5 months), middle-aged (18-19), and old (24-25 months) F344BNF1 hybrid rats. We observed that old F344BNF1 rats exhibited decreased motoric performance, and lower levels of spontaneous and D- amphetamine-induced locomotor activity than those observed in young F344BNF1 rats. Microdialysis measures of extracellular basal levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), and 4-hydroxy-3-methoxyphenylacetic acid (HVA) were significantly diminished in the striata of the middle-aged and old rats as compared to levels in young animals. In addition, D- amphetamine-evoked overflow of DA was significantly decreased in the middle- aged and aged rat striatum as compared to DA overflow in young F344BNF1 rats. Studies of postmortem brain tissue showed that the changes in overflow of DA correlated with significantly lower DA tissue content in ventral striatum and midbrain. Moreover, both dopamine turnover ratios (DOPAC/DA, HVA/DA) and the serotonin turnover ratio (5-HIAA/5-HT) were significantly elevated in the ventral striatum and nucleus accumbens. The results of this study demonstrate a correlation between reductions in striatal DA neurochemistry and diminished motor function in aged F344BNF1 rats.

Original languageEnglish
Pages (from-to)246-256
Number of pages11
JournalBrain Research
Volume791
Issue number1-2
DOIs
StatePublished - Apr 27 1998

Bibliographical note

Funding Information:
We would like to thank Shane Delinks for his assistance with the measurements of monoamines and metabolites in brain tissues. This research was supported by PHS grants NS09199 and AG06434 (GAG) and the NIA Pilot Program (DMY).

Keywords

  • 3,4-Dihydroxyphenylacetic acid
  • 4-Hydroxy-3-methoxyphenylacetic acid
  • Aging
  • D-amphetamine
  • F344BNF rat
  • Microdialysis

ASJC Scopus subject areas

  • Neuroscience (all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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