Aged Fischer 344 rats exhibit altered locomotion in the absence of decreased locomotor activity: exacerbation by nomifensine John A. Stanford a,b,c, * , Elena Vorontsova d , Stewart P. Surgener a,b,c , Greg A. Gerhardt a,b,c,e , Stephen C. Fowler d a Department of Anatomy and Neurobiology, University of Kentucky Chandler Medical Center, Lexington, KY, USA b Center for Sensor Technology, University of Kentucky Chandler Medical Center, Lexington, KY, USA c MorrisK.UdallParkinson’sDiseaseResearchCenterofExcellence,UniversityofKentuckyChandlerMedicalCenter,Lexington,KY,USA d Departments of Human Development, Pharmacology and Toxicology, and The Schiefelbusch Institute for Life Span Studies, University of Kansas, Lawrence, KS, USA e Department of Neurology, University of Kentucky Chandler Medical Center, Lexington, KY, USA Received 25 May 2002; received in revised form 12 August 2002; accepted 12 September 2002 Abstract A novel force plate actometer was used to measure locomotor activity and gait in young (6 months) versus aged (24 months) Fischer 344 rats. The actometer revealed altered gait in the aged rats in the absence of decreased locomotor activity. The catecholamine uptake inhibitor, nomifensine increased locomotor activity in both groups and exacerbated the gait alteration in the aged group. Analyses of whole brain tissue levels of dopamine (DA), 3,-4 dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in the substantia nigra and dorsal striatum revealed no significant differences between the two age groups. In the young (but not aged) rats, distance traveled was negatively correlated with striatal DOPAC 1 HVA/DA tissue ratios (a measure of DA turnover). In the aged (but not the young) rats, positive correlations were observed between distance traveled and DOPAC 1 HVA/DA ratios in the substantia nigra. Neither striatal nor nigral DA content was significantly correlated with distance traveled in either age group. These findings demonstrate that aged rats may exhibit functional changes in locomotor activity in the absence of quantitative changes in nigrostriatal DA content. q 2002 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Aging; Movement; Gait; Dopamine; Basal ganglia Normal aging in humans and in animals is often asso- ciated with bradykinesia, or a marked deterioration in both the quantity and speed of motor activity [11,13]. Gait abnormalities are also common in human aging and are associated with increased morbidity in the elderly [1,13]. The fact that these deficits are also prevalent in Parkinson’s disease (PD) [5] suggests that diminished nigrostriatal dopa- mine (DA) function may play a role in their occurrence. There is substantial evidence from animal studies support- ing this hypothesis as it relates to bradykinesia (e.g. Ref. [11]). In contrast, quantifying gait in rats is laborious (e.g. Refs. [3,18,19]) and a role for altered DA function in age- related gait disturbances remains to be examined in animal models of normal aging. Although the pronounced gait disturbances that are observed in PD (e.g. Ref. [14]) and in the Albino Swiss agu mutated rat [2] support a relation- ship between nigrostriatal DA function and gait, the changes in gait that are observed in normal aging have generally been attributed to cerebellar or peripheral mechanisms [3,19]. These previous studies did not, however, directly quantify relationships between motor and nigrostriatal neurochemical measures. The purpose of the present study was to examine quanti- tative (distance traveled) and qualitative (gait) differences in locomotor activity between young and aged Fischer 344 (F344) rats using a newly-developed force-plate actometer [6]. Because some studies have demonstrated that aged rats exhibit diminished locomotor activity only after habituation (e.g. Ref. [8]), we wanted to determine whether the actometer would reveal altered patterns of locomotion in aged rats, even if changes in distance traveled were not Neuroscience Letters 333 (2002) 195–198 0304-3940/02/$ - see front matter q 2002 Elsevier Science Ireland Ltd. All rights reserved. PII: S0304-3940(02)01105-9 www.elsevier.com/locate/neulet * Corresponding author. 312 Davis Mills Building, University of Kentucky, Lexington, KY 40536-0098, USA. Tel.: 11-859-323- 1724; fax: 859-257-5310 E-mail address: jastan2@pop.uky.edu (J.A. Stanford).