Behavioral models of Parkinson's disease in rodents: a new look at an old problem

Abstract

The circuitry important for voluntary movement is influenced by dopamine from the substantia nigra and regulated by the nigrostriatal system. The basal ganglia influence the pyramidal tract and other motor systems, such as the mesopontine nuclei and the rubrospinal tract. Although the neuroanatomical substrates underlying motor control are similar for humans and rodents, the behavioral repertoire mediated by those circuits is not. The principal aim of this review is to evaluate how injury to dopamine-mediated pathways in rodents gives rise to motor dysfunction that mimics human Parkinsonism. We will examine the behavioral tests in common use with rodent models of Parkinson's disease and critically evaluate the appropriateness of each test for detecting motor impairment. We will show how tests of motor performance must be guided by a thorough understanding of the clinical symptoms accompanying the disease, the circuitry mediating dopamine deficits in rodents, and familiarity with the rodent behavioral repertoire. We will explain how investigations in rodents of skilled forepaw actions, including placing, grooming, or foot faults, have clear correlates in Parkinson's disease, and are, therefore, the most sensitive ways of detecting motor impairment following dopamine loss from the basal ganglia of rodents.