Age-related reductions in [3H]WIN 35,428 binding to the dopamine transporter in nigrostriatal and mesolimbic brain regions of the fischer 344 rat

Meleik A. Hebert, Gaynor A. Larson, Nancy R. Zahniser, Greg A. Gerhardt

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44 Scopus citations

Abstract

In the present study, we used the potent cocaine analog [3H]WIN 35,428 to map and quantify binding to the dopamine transporter (DAT) within the dorsal striatum, nucleus accumbens, substantia nigra, and ventral tegmental area in young (6-month-old), middle-aged (12-month-old), and aged (18- and 24-month-old) Fischer 344 rats. Quantitative autoradiographic analysis of indirect [3H]WIN 35,428 saturation curves revealed two-site binding for all four brain regions in every age group. The percentage of binding to the high- or low-affinity sites did not differ with age or region and was approximately 50%. However, significant age-related decreases in the overall density (B(max)) of [3H]WIN 35,428-binding sites were observed in the striatum, nucleus accumbens, substantia nigra, and ventral tegmental area. The B(max) within all brain regions declined by more than 15% every 6 months, with the B(max) in the aged (24-month-old) group being approximately half that measured in the young adult (6-month-old) group. Competition experiments indicated that nomifensine also exhibited two-site binding to the DAT in Fischer 344 rats. No consistent age-related differences in binding affinities were noted with either [3H]WIN 35,428 or nomifensine. Taken together, these results support the hypothesis that functional DATs within the nigrostriatal and mesolimbic systems are down-regulated with age, without changing their affinity for ligands.

Original languageEnglish
Pages (from-to)1334-1339
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume288
Issue number3
StatePublished - Mar 1999

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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