L-DOPA inhibits depolarization-induced [3H]GABA release in the dopamine-denervated globus pallidus of the rat: the effect is dopamine independent and mediated by D2-like receptors.
The effect of L-DOPA on [(3)H]GABA release in slices of globus pallidus from 6-OHDA-lesioned rats was studied. Release was evoked by high (15 mM) K(+). The lesion reduced dopamine content and dopamine synthesized from L-DOPA. The inhibition of DOPA decarboxylase blocked dopamine synthesis. Endogenous dopamine released by high K(+) inhibited [(3)H]GABA release in normal but not in lesioned slices. L-DOPA inhibited (IC(50) = 0.44 microM) evoked [(3)H]GABA release. The inhibition was via D2-like receptors but not mediated by dopamine. The turning behavior induced by L-DOPA methyl ester (25 mg/kg, i.p.) was not abolished by the DOPA decarboxylase inhibitor 3-hydroxybenzylhydrazine but in this condition it was abolished by sulpiride. Results suggest that L-DOPA acting as D2-like agonist inhibits GABA release in the rat globus pallidus and induces turning behavior in rats with unilateral lesions of the dopamine innervation. L-DOPA could control Parkinson's disease symptoms acting not only as dopamine precursor but also by itself.
Silva
I
I
Departamento de Fisiología, Biofísica y Neurociencias del CINVESTAV, México, México.
Cortes
H
H
Escartín
E
E
Rangel
C
C
Florán
L
L
Erlij
D
D
Aceves
J
J
Florán
B
B
D000818:Animals; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D003627:Data Interpretation, Statistical; D003653:Decarboxylation; D003714:Denervation; D004298:Dopamine / Q000502:physiology*; D015259:Dopamine Agents / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005917:Globus Pallidus / Q000187:drug effects / Q000378:metabolism*; D006834:Hydrazines / Q000494:pharmacology; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D008474:Medial Forebrain Bundle / Q000502:physiology; D016627:Oxidopamine; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D013239:Stereotyped Behavior / Q000187:drug effects; D013469:Sulpiride / Q000494:pharmacology; D013563:Sympathectomy, Chemical; D013565:Sympatholytics; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D015259:Dopamine Agents; D018492:Dopamine Antagonists; D004791:Enzyme Inhibitors; D006834:Hydrazines; D017448:Receptors, Dopamine D2; D013565:Sympatholytics; D007980:Levodopa; D005680:gamma-Aminobutyric Acid; D013469:Sulpiride; D016627:Oxidopamine; C004297:3-hydroxybenzylhydrazine; D011188:Potassium; D004298:Dopamine