Relationship between sensorimotor neglect and the specificity, degree and locus of mesotelencephalic dopaminergic cell loss following 6-hydroxydopamine.

The involvement of cell groups within the dopaminergic mesotelencephalic system in the development of the sensorimotor neglect syndrome was re-evaluated in two ways. Firstly, dopaminergic specificity of the neglect was further established by studying the relationship between nomifensine protection of dopamine cells against 6-hydroxydopamine damage and the degree of neglect which resulted. The sensorimotor neglect syndrome which developed following injection of 6-hydroxydopamine was diminished by concomitant treatment with nomifensine in parallel with the degree of protection afforded the dopaminergic cells. Non-specific damage produced by 6-hydroxydopamine was unaltered by nomifensine. Secondly, the role in sensorimotor neglect of both total cell damage, and damage to regional sub-classes of dopaminergic cells was considered. It was found that the extent of the resulting neglect was correlated with the overall damage to the substantia nigra and ventral tegmental area, rather than to any individual region within this dopaminergic system. There was a threshold, involving destruction of approximately one third of the system, below which no neglect syndrome developed. Certain regions, including the ventral tegmental area (VTA), showed a higher partial correlation with the extent of neglect than other regions. While specific lesioning of the A8 or A10 dopaminergic neurons is probably insufficient to produce a neglect syndrome, damage to these areas potentiates the severity of the neglect produced by nigrostriatal lesions. It appears that the involvement of the individual subclasses of the mesotelencephalic dopaminergic neurons in the neglect syndrome is more widespread than previously thought.