Behavioral and neurochemical dynamics of neurotoxic meso-striatal dopamine lesions

Here we review some of our recent experiments where the neurotoxin 6-hydroxydopamine had been used to unilaterally damage nigro-striatal dopamine neurons in the rat. In this lesion model we studied relationships between the degree of neostriatal dopamine loss, the resulting behavioral deficits, possible recovery therefrom, and mechanisms which may be related to such recovery. Special attention is given to animals with more moderate dopamine lesions, since these may be particularly suitable to study functional recovery. Our behavioral studies showed that initially after lesion (day 1), asymmetries of turning and scanning behavior were observed over a wide range of neostriatal DA depletions, whereas after one week these had recovered to symmetry except in animals with residual neostriatal dopamine levels of 20% or less. Subsequent experiments showed that behavioral asymmetries can also be induced in animals with less severe lesions (residual DA levels 45-65%), since ipsiversive asymmetries in scanning and turning were observed when such animals were challenged systemically with the mixed dopamine receptor agonist apomorphine. Finally, a weak ipsiversive asymmetry could also be induced in such animals by the more selective D2-agonist LY171555, whereas the D1-agonist SKF38393 was ineffective. These results are discussed with respect to the neural mechanisms determining deficits and recovery after such dopamine lesions and their relevance to similar clinical phenomena, namely Parkinson's disease. Here, special attention is given to the role of mechanisms, which can regulate compensatory increases of dopamine activity in those neurons which have survived the lesion.