FORELIMB AKINESIA IN THE RAT PARKINSON MODEL - DIFFERENTIAL-EFFECTS OF DOPAMINE AGONISTS AND NIGRAL TRANSPLANTS AS ASSESSED BY A NEW STEPPING TEST

Methods for the assessment of akinesia in the unilateral rat Parkinson model have so far been lacking, The experiments reported here evaluat e the usefulness of a new ''stepping test'' to monitor forelimb akines ia in rats with unilateral 6-hydroxydopamine (6-OHDA) lesions of the m esencephalic dopamine (DA) system, and to assess the ability of DA-rec eptor agonists and fetal DA neuron transplants to reverse these defici ts, The 6-OHDA lesion induced marked and long-lasting impairments in t he initiation bf stepping movements with the contralateral paw, System ic injections of low doses (chosen to be subthreshold for induction of rotation) of the mixed D1 and D2 receptor agonist apomorphine, the D1 -selective agonist SKF 38393, and to a lesser extent also the DP-selec tive agonist quinpirole were effective in reversing these deficits, Si milar effects was seen after a subrotational dose of L-dopa, whereas a mphetamine had no effect, Fetal nigral transplants, implanted as multi ple deposits in the ipsilateral caudate-putamen and substantia nigra, restored initiation of stepping to a similar degree as the DA agonists , Nigral grafts placed in substantia nigra alone were also effective, although the improvement was less pronounced, Apomorphine, at a dose e ffective in the lesion-only animals, had no additive effect in the gra fted rats, whereas amphetamine appeared to further improve stepping in the rats with intranigral transplants, identical experiments were per formed on skilled forelimb use in the so-called staircase test. Intere stingly, neither the DA agonist drugs nor the nigral transplants had a ny effects on the lesion induced deficits in this more complex task, T he results show that forelimb stepping is a highly useful test to moni tor lesion-/and transplant-induced changes in forelimb akinesia, a beh avioral parameter that may be analogous to limb akinesia and gait prob lems seen in patients with Parkinson's disease.