DIFFERENTIAL RECOVERY OF VOLITIONAL MOTOR FUNCTION, LATERALIZED COGNITIVE FUNCTION, DOPAMINE AGONIST-INDUCED ROTATION AND DOPAMINERGIC PARAMETERS IN MONKEYS MADE HEMI-PARKINSONIAN BY INTRACAROTID MPTP INFUSION

There is still controversy regarding the fequency and extent of spontaneous functional recovery in primate models of parkinsonism, perhaps in part stemming from the variety of ways in which recovery has been assessed. The present study examined functional recovery in monkeys made unilaterally parkinsonian by intracarotid infusion of MPTP. Monkeys were evaluated prior to lesioning and for at least 1 year after lesioning on a battery of tests including a rating of spontaneous behaviors, a learned reaction time/movement time task, tests of lateralized neglect or inattention (i.e. lateralized reward retrieval task, extinction with double simultaneous stimulation, and response to a target moving from one hemispace to the other), and rotational asymmetry in response to a dopamine agonist, Some animals also received 6-[F-18]Fluoro-L-Dopa (F-DOPA) positron emission tomography (PET) scans before MPTP, when symptomatic, and when showing signs of functional recovery. These animals were sacrificed for post mortem neurochemical assessment following the last PET scan. Results showed that estimates of functional recovery in hemi-parkinsonian monkeys may depend upon the behavioral assay used. Even in behavioral tasks that were sensitive to recovery effects, the degree of functional recovery shown by an animal on one such task did not predict recovery on another. This may in part be due to the inherent difficulty in designing behavioral tests to assess basal ganglia functioning, when there is no consensus concerning which aspects of behavior the normal basal ganglia actually control. The results also suggest that the relationship of post-mortem striatal dopamine levels or in vivo estimates of pre-synaptic dopaminergic function to functional recovery are also tenuous. The hemi-parkinsonian monkey is a valuable but complex behavioral model and care needs to be taken in assessing functional impairment and functional recovery in such animals.