6-hydroxydopamine-induced degeneration of the nigrostriatal dopamine pathway: the turning syndrome.

UNILATERAL injection of 6-hydroxydopamine (6-OH-DA) into the dopamine (DA) cell bodies in the substantia nigra of a rat induces a degeneration of the entire nigro-striatal DA neuron system (Ungerstedt, 1968, 1971a). The lesion causes the animal to deviate in movements and posture towards the lesioned side (Ungerstedt, 1968, 1971b). Due to the high specificity of the 6-OH-DA induced lesion (Ungerstedt, 1971a; H6kfelt and Ungerstedt, 1973) the change in motor behavior is in all probability an expression of the imbalance in DA transmission induced by the unilateral lesion. An increase in DA transmission in the remaining DA system, e.g. by DA-releasing drugs, induces a circling movement , a rotation, towards the lesioned side. This rotation may be recorded in a ' rotometer ' (Ungerstedt and Arbuthnott , 1970), where the animal is connected by a thin wire to a recording device and allowed to move around freely within a plexi-glass bowl, shaped as a hemisphere. Drug induced rotational behavior is clearly dose-dependent indicating that the intensity of the rotation is quantitatively related to DA transmission (Ungerstedt, 1971b, c). Rotational behavior may be used as a model to study several functional aspects of the nigro-striatal DA neurons and the basal ganglia. The following outlines the principal findings after treatment with preand postsynaptically acting drugs as well as some theoretical considerations regarding the basal ganglia, their afferents and efferents. The findings with the '6-OH-DA rotational model ' has several implications for clinical studies. The model may for instance, be used to evaluate drugs potentially useful in the treatment of Parkinson's disease.