of review provided by Aboagye andcolleagues is a good early step in thisdirection.

David A. Mankoff, Jeanne M. Link,Jashvant Unadkat, Janet F. Eary,

Kenneth A. KrohnDivision of Nuclear Medicine and Department

of PharmaceuticsUniversity of Washington

Seattle, WA, USA

References01 Aboagye, E.O. et al. (2001) In vivo

pharmacokinetics and pharmacodynamics indrug development using positron-emissiontomogoraphy. Drug Discov. Today 6, 293–302

02 Tewson, T. and Krohn, K.A. (1998) PETradiopharmaceuticals: state-of-the-art andfuture prospects. Semin. Nucl. Med. 28,221–234

03 Mankoff, D.A. and Bellon, J.R. (2001) PETimaging of cancer: FDG and beyond. Semin.Rad. Oncol. 11, 16–27

04 Hoffman, J.M. (2000) Imaging in cancer: aNational Cancer Institute ‘extraordinaryopportunity’. Neoplasia 2, 5–8

05 O’Sullivan, F. (1993) Imaging radiotracermodel parameters in PET: a mixture analysisapproach. IEEE Trans. Med. Imag. 12, 399–412

06 Cunningham, V. and Jones, T. (1993) Spectralanalysis of dynamic PET studies. J. Cereb.Blood Flow Metab. 13, 15–23

Are drug targets missed dueto lack of physical activity? –Reply ▲▲

Initial letter: Gurwitz, D. (2001) DrugDiscov. Today 6, 342–343Response from Brenda Anderson

David Gurwitz provides goodjustification for testing drug efficacy inexercising rodents. He rightfully pointsout that the genome is ‘fine-tuned’ forphysical activity, and provides evidencethat exercise influences many systems,including transmitter systems1–3.

Despite the evidence, the use ofexercising rats might not be appropriatefor all drug testing. Numerous humanconditions and disease states areassociated with reduced levels of activity.

Individuals that develop Alzheimer’sdisease are reported to lead moresedentary lives prior to disease onsetrelative to persons that do not go on todevelop the disease4. Low levels ofphysical activity are associated withbouts of depression, and activity isreduced with age. Thus, specificconditions exist that might be modeledbest with the standard lab cage.

Although it might be true (as Gurwitzpoints out) that drug efficacy could bebetter detected in exercising rats,sedentary rats might provide a bettermodel for the detection of side effects.Exercise can be neuroprotective againstischemia5 and epilepsy6–7. Exercising ratshave less oxidative damage in the brain8,and an increased capacity for oxidativemetabolism in central motor structures9.Therefore, side effects related toexcitotoxicity could be detected moreeasily in sedentary rather than inexercising rodents.

Strong arguments can be made forthe use of exercise as a standardlaboratory condition. However, theultimate choice of animal housingshould depend on the population beingmodeled, and the goal of the study.

References01 Brown, B.S. and Van Huss, W. (1973) Exercise

and rat brain catecholamines. J. Appl. Physiol.34, 664–669

02 Fordyce, D.E. and Farrar, R.P. (1991) Physicalactivity effects on hippocampal and parietalcortical cholinergic function and spatiallearning in F344 rats. Behav. Brain Res. 43,115–123

03 MacRae, P.G. et al. (1987) Endurance trainingeffects on striatal D2 dopamine receptorbinding and striatal dopamine metabolitelevels. Neurosci. Lett. 79, 138–144

04 Friedland, R.P. et al. (2001) Patients withAlzheimer’s disease have reduced activities inmidlife compared with healthy control-groupmembers. Proc. Natl. Acad. Sci. U. S. A. 98,3440–3445

05 Stummer, W. et al. (1994) Reduced mortalityand brain damage after locomotor activity ingerbil forebrain ischemia. Stroke 25, 1862–1869

06 Arida, R.M. et al. (1998) Effect of physicalexercise on kindling development. EpilepsyRes. 30, 127–132

07 Arida, R.M. et al. (1999) Effect of physicalexercise on seizure occurrence in a model oftemporal lobe epilepsy in rats. Epilepsy Res.37, 45–52

08 Radák, Z. et al. (2001) Regular exerciseimproves cognitive function and decreasesoxidative damage in rat brain. Neurochem. Int.38, 17–23

09 McCloskey, D.P. et al. (2001) Exerciseincreases metabolic capacity in the motorcortex and striatum, but not in thehippocampus. Brain Res. 891, 168–175

Brenda AndersonDepartment of Psychology

State University of New York at Stony BrookStony Brook, NY 11794, USA

DDT Vol. 6, No. 10 May 2001 updatediscussion forum

1359-6446/01/$ – see front matter ©2001 Elsevier Science Ltd. All rights reserved. PII: S1359-6446(01)01798-6 515

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