[Choreic movements and dopamine--implications to the underlying neural mechanisms involved]

Choreic movement is one of the most attractive involuntary movements in terms of searches for the underlying mechanisms. Huntington's disease is a most popular disorder exhibiting choreic movements, in which the rather selective striatal degeneration is postulated to be responsible for the generation of choreic movements. In this respect, we have recently produced an experimental model of choreic movements in monkey by combined methods of kainic acid injection into the unilateral striatum and the oral administration of L-DOPA. The purpose of this paper is to summarize our experiment and to review the previous papers on experimental model of choreic movements in order to shed light on the underlying mechanisms of choreic movements. There are at least following three possible mechanisms in the generation of choreic movement. 1) A massive loss of GABAergic inhibitory neurones in the striatum induces disinhibitory effects on nigral dopaminergic neurones, which causes activation of dopaminergic neurones and choreic movements. However, a loss of GABA in the nigra does not always correlate with the generation of choreic movements. 2) A hypersensitive receptors for dopamine in the striatum may cause choreic movements. In fact, however, dopamine receptors are decreased or normal rather than increased not only in Huntington's disease but also in monkey models. 3) A massive loss of neurones in the striatum causes a loss of post-synaptic components of dopaminergic terminals. This may further cause rearrangements and compensatory changes in dopaminergic terminals in the spared striatum. These changes may activate pre-synaptic dopaminergic components which are further activated by the administration of L-DOPA. This hypothesis is mainly derived from the experimental model in monkey.