NORMAL AND DRUG-INDUCED LOCOMOTOR BEHAVIOR IN AGING - COMPARISON TO EVOKED DA RELEASE AND TISSUE CONTENT IN FISCHER-344 RATS

The consequences of aging on dopamine (DA) regulation within the nigro striatal and mesolimbic systems were investigated with a combination o f behavioral, in vivo electrochemical, and high-performance liquid chr omatography measurements using 6-, 12-, 18- and 24-month old male Fisc her 344 (F344) rats. Spontaneous locomotor testing demonstrated that a ged (18- and 24-month) rats moved significantly less and at a slower s peed than younger (6- and 12-month) animals. Additionally, systemic in jection (intraperitoneal) of the DA uptake inhibitor, nomifensine, was significantly less efficacious in augmenting the locomotor activity o f aged rats compared to the younger animals. Age-dependent alterations in the release capacity of DA neurons within the regions involved in movement were investigated using in vivo electrochemistry. These recor dings indicated that both the magnitude and temporal dynamics of potas sium (70 mM)-evoked DA overflow were affected by the aging process. Si gnal amplitudes recorded in the 24-month rats were 30-60% reduced in b oth the striatum and nucleus accumbens as compared to the young adult groups. In addition, the duration of the electrochemical DA signals re corded within the striatum of 24-month old rats was twice that in the younger animals (6- and 12-month). Whole tissue measurements of DA and DA metabolites suggest age-related deficits in locomotion and DA rele ase were not related to decreases in the storage or synthesis of DA wi thin the striatum, nucleus accumbens, substantia nigra, Ventral tegmen tal area or medial prefrontal cortex. Taken together, these results in dicate age-dependent deficits in movement are related ro the dynamic p roperties of DA release and not static measures of DA content. (C) 199 8 Elsevier Science B.V. All rights reserved.