Abstract
Age-related changes in the capacity, rate, and modulation of dopamine (DA) uptake within the striatum and the nucleus accumbens core of Fischer 344 rats were investigated using in vivo electrochemical recordings coupled with local drug application techniques. Equimolar amounts of DA were pressure ejected into the striatum and the nucleus accumbens of 6-, 12-, 18-, and 24-month old rats. The DA ejections produced larger DA signal amplitudes in the older rats, suggesting age-related differences in the capacity to clear extracellular DA. Within the striatum, the capacity and rate of DA uptake were reduced by 50% in the aged groups (18 and 24months) compared with the younger rats (6 and 12 months). In the nucleus accumbens, significant reductions in DA uptake capacity and rate were observed in the 24-month group. In both brain regions and in all age groups studied, the rate of DA uptake was found to be concentration-dependent until a maximal rate was reached. The maximum rate of DA transport was significantly reduced in both the striatum and the nucleus accumbens of aged rats (18 and 24 months versus 6 and 12 months). The ability of nomifensine, an inhibitor of the DA transporter, to modulate DA signal amplitudes in the striatum and the nucleus accumbens was also decreased with age (24 months versus 6 months). Taken together, these findings demonstrate substantial age-related deficits in DA uptake processes within the striatum and the nucleus accumbens, consistent with the hypothesis that DA uptake may be slowed in aged animals to compensate for reductions in DA release.
Footnotes
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Send reprint requests to: Greg A. Gerhardt, Ph.D., Department of Psychiatry, Box C268-71, University of Colorado Health Sciences Center, 4200 East Ninth Ave., Denver, CO 80262. E-mail:Greg.Gerhardt{at}uchsc.edu
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↵1 This work was supported by grants from U.S. Public Health Services Grants NS09199 and AG06434 and National Institutes of Health Training Grant HDO7408-02. In addition, this work was supported, in part, by a Level II Research Scientist Development Award (MH01245) from the National Institutes of Mental Health to G. Gerhardt.
- Abbreviations:
- DA
- dopamine
- DAergic
- dopaminergic
- DAT
- dopamine transporter
- F344
- Fischer 344
- NET
- norepinephrine transporter
- SERT
- serotonin transporter
- DOPAC
- 3,4-dihydroxyphenylacetic acid
- Tc
- clearance rate
- T20
- time for signal amplitude to decay by 20%
- T60
- time for signal amplitude to decay by 60%
- ANOVA
- analysis of variance
- Received July 10, 1998.
- Accepted September 8, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
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