EXPERIMENTAL BASIS OF THERAPY OF PARKINSONS-DISEASE AND CHOLINERGIC-DOPAMINERGIC EQUILIBRIUM IN BASAL BRAIN NUCLEI

The simple scheme of a closed loop of interactions between nigro-neostriatal and strio-nigral pathways is obsolete and insufficient. [Studies in rats and rabbits are described.] The striatum is not the sole target point of apomorphine stereotypy, but is only 1 of the components of a complicated, multineuronal circuit. Apomorphine-induced stereotypy is not a unitary phenomenon, and its individual components (gnawing, licking and sniffing) depend on various structures of the brain; the description of the intensity of stereotypy by simple summation of scores used popular scales is unjustified, and may be misleading. The structures responsible for spiroperidol-induced catalepsy are different from the structures responsible for apomorphine stereotypy. The cholinergic system of the striatum of the rabbit acts synergistically with, rather than antagonistically to, dopamine receptors. This suggests that the striatum is not the anatomical pivotal point of cholinergic-dopaminergic equilibrium in the aspect of clinical effects of drugs efficient in the treatment of extrapyramidal disturbances including [human] Parkinson''s disease. Cholinergic and dopaminergic systems in the substantia nigra are mutually antagonistic. The substantia nigra may be 1 of the structures which is a central point of cholinergic-dopaminergic equilibrium. The cholinergic-dopaminergic equilibrium results rather from complex interrelations of mutual stimulations and inhibitions of these systems, localized in several anatomical structures, than on the effect of drugs used for the therapy of Parkinson''s disease on one structure only. There is no definite anatomical pivotal point for the cholinergic-dopaminergic equilibrium. Cholinoceptive cells of the reticular part of substantia nigra are predominantly present in its lateral part, and transmit impulses through the nigro-thalamic pathway to caudatus nucleus and cerebral cortex, and possibly also to other structures of the multineuronal circuit responsible for extrapyramidal functions. The substantia nigra contains 2 functionally different acetylcholine receptors. The cholinergic receptors in substantia nigra probably cannot be classified similarly to cholinergic peripheral receptors, but display simultaneously the properties of both muscarinic and nicotinic receptors.