A 6-HYDROXYDOPAMINE-INDUCED SELECTIVE PARKINSONIAN RAT MODEL - FURTHER BIOCHEMICAL AND BEHAVIORAL CHARACTERIZATION

The main focus of the present study was to define the rotational respo nse of 6-hydroxydopamine-lesioned rats to dopaminergic agonists to sep arate the partially lesioned rats from those having complete substanti a nigra (SN) and ventral tegmental area (VTA) lesions. Animals were ch allenged by amphetamine and L-DOPA for 10 consecutive weeks. There was a correlation between rotational behavior and extent of midbrain cell loss. Rats with complete SN and < 40% VTA lesion turned more than 5 t imes/min after amphetamine administration, but not after L-DOPA; anima ls with complete SN and 40-80% VTA lesions turned vigorously following amphetamine and began turning after L-DOPA administration. Rats with complete SN and VTA lesions turned less after amphetamine than the oth er two groups, while their turning after L-DOPA administration increas ed. Extracellular dopamine (DA) measured by microdialysis, intracellul ar DA measured by postmortem tissue punches, and tyrosine hydroxylase- immunoreactive cell count in SN and VTA were also evaluated. It appear s that the dopaminergic cells in the lateral VTA affect DA concentrati on in the medial caudate nucleus. In the nucleus accumbens of the lesi oned side, DA release and metabolism substantially increased with the larger VTA lesion. Dopamine turnover rate in the caudate was also high er in the group with < 40% VTA lesion. (C) 1994 Academic Press, Inc.