BIOCHEMICAL AND ANATOMICAL CHARACTERIZATION OF FOREPAW ADJUSTING STEPS IN RAT MODELS OF PARKINSONS-DISEASE - STUDIES ON MEDIAL FOREBRAIN-BUNDLE AND STRIATAL LESIONS

Deficits in forepaw adjusting steps in rats have been proposed as a no n-drug-induced model of the akinesia associated with Parkinson's disea se. The present study examined the relationship between contralateral forepaw adjusting steps and dopamine depletion after medial forebrain bundle lesions with 6-hydroxydopamine. Depletion of striatal dopamine by >80% resulted in dramatic reductions in the ability of rats to make adjusting steps, but rats with <80% dopamine depletion had no detecta ble deficit. The deficit in forepaw adjusting steps was evident by thr ee days after lesions and did not recover for up to 13 weeks. Compared to apomorphine-induced rotation, the deficit in adjusting steps was e vident at milder dopamine depletion. Discrete striatal lesions were al so utilized to localize the striatal subregions that mediate forepaw a djusting steps. Forepaw adjusting steps were reduced after lesions of dorsolateral, ventrolateral or ventrocentral striatum, but not after l esions of dorsomedial, dorsocentral or ventromedial striatum. The redu ctions in adjusting steps after the discrete striatal lesions were not as severe as after medial forebrain bundle lesions. Furthermore, none of the discrete striatal lesions resulted in rotation after apomorphi ne administration, although a few resulted in increase in amphetamine- induced rotation. Administration of L-3,4-dihydroxyphenylalanine parti ally reversed the reductions of forepaw adjusting steps in both sets o f lesion experiments. Together, these results suggest that forepaw adj usting step deficits in the rat provide a good model for the akinesia of Parkinson's disease both in medial forebrain bundle and striatal le sions, and would be a useful tool for investigating the efficacy of va rious therapeutic strategies. (C) 1998 IBRO. Published by Elsevier Sci ence Ltd.