Striatal dopamine depletion, dopamine receptor stimulation, and GABA metabolism: implications for the therapy of Parkinson's disease.
Dopamine-denervated rat striata exhibit increased synaptosomal gamma-aminobutyric acid (GABA) synthetic capacity (glutamate decarboxylase activity) without an alteration in GABA transport capacity. Stimulating denervated striatal dopamine receptors with apomorphine selectively increases in vivo steady-state striatal GABA turnover. The striatal response in animals to isolated loss of dopamine innervation is an increase in glutamate decarboxylase activity, not the decrease frequently found in the brains of patients with Parkinson's disease. Neurochemical expression of denervated striatal dopamine receptor stimulation may involve increased synaptic activity of striatal GABA neurons. For these reasons, enhancement of basal ganglia GABA function may improve responsiveness to dopamimetic therapies in patients with Parkinson's disease.
Bennett
J P
JP
D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000032:analysis*; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006892:Hydroxydopamines; D016627:Oxidopamine; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D006892:Hydroxydopamines; D011954:Receptors, Dopamine; D005680:gamma-Aminobutyric Acid; D016627:Oxidopamine; D005968:Glutamate Decarboxylase; D004298:Dopamine