The neuropathology of GABA neurons in extrapyramidal disorders.

Dysfunction of neurons in the extrapyramidal system (EPS) which use GABA as their neurotransmitter can be noted in both degenerative diseases of the EPS and in iatrogenic (i.e. drug-induced)disorders of EPS function. In Huntington's chorea there is a loss of both GABA neurons and GABA receptors in the striatum; those remaining GABA receptors likely have an altered kinetic profile, with a higher affinity for GABA than the receptors found in the non-Huntington's brain. In Parkinson's disease the lower levels of L-glutamic acid decarboxylase observed in the EPS is likely not associated with neuronal cell loss but is likely secondary to the dopamine neuron loss. These alterations in GABA neuron function and the long-term changes associated with chronic L-DOPA therapy may be related to Parkinsonian tremor. The drug-induced dyskinesias (L-DOPA, neuroleptic) appear to be associated with a relative hypo-function of EPS GABA neurons, especially in relation to DA neuron function, whereas in the case of drug-induced Parkinsonism the opposite may be the case. The function and dysfunction of GABA neurons in the EPS cannot be seen as a separate entity, but must be considered in relation to alterations in other EPS neurons, especially dopamine and acetylcholine.