Normal and drug-induced locomotor behavior in aging: comparison to evoked DA release and tissue content in fischer...

The consequences of aging on dopamine (DA) regulation within the nigrostriatal and mesolimbic systems were investigated with a combination of behavioral, in vivo electrochemical, and high-performance liquid chromatography measurements using 6-, 12-, 18- and 24-month old male Fischer 344 (F344) rats. Spontaneous locomotor testing demonstrated that aged (18- and 24-month) rats moved significantly less and at a slower speed than younger (6- and 12-month) animals. Additionally, systemic injection (intraperitoneal) of the DA uptake inhibitor, nomifensine, was significantly less efficacious in augmenting the locomotor activity of 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 recordings indicated that both the magnitude and temporal dynamics of potassium (70 mM)-evoked DA overflow were affected by the aging process. Signal amplitudes recorded in the 24-month rats were 30-60% reduced in both the striatum and nucleus accumbens as compared to the young adult groups. In addition, the duration of the electrochemical DA signals recorded 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 release were not related to decreases in the storage or synthesis of DA within the striatum, nucleus accumbens, substantia nigra, ventral tegmental area or medial prefrontal cortex. Taken together, these results indicate age-dependent deficits in movement are related to the dynamic properties of DA release and not static measures of DA content.