GABA receptor binding in rat striatum: localization and effects of denervation.
Intrastriatal injection of 2 microgram of kainic acid, a conformationally restricted analogue of glutamate, causes degeneration of GABAergic neurons intrinsic to the striatum while sparing axons of extrinsic neurons terminating in or passing through the region. From 2 to 15 days after striatal lesion with kainate, the sodium-independent binding of [3H]-psi-aminobutyric acid (GABA) to striatal membranes is increased 200% above that of control. Differences in the amount of endogenous GABA contaminating the membrane preparations do not account for the increased receptor binding. Scatchard analysis reveals an increased affinity of the GABA receptor in the kainate-lesioned striatum with no change in the number of binding sites. The subcellular distribution of the receptor as well as the sensitivity of the receptor to several agonists and antagonists is unchanged by the kainate lesion. Ablation of the nigrostriatal dopaminergic pathway by nigral injection of 8 microgram of 6-hydroxydopamine reduces by 22% the specific binding of [3H]GABA in the ipsilateral striatum and attenuates by 33% the increase in GABA receptor binding produced by the striatal kainate lesion. These studies demonstrate that (1) the sodium independent binding sites for GABA in striatum are localized on axons of extrinsic neurons, and (2) the affinity of these receptors for GABA increases in response to GABAergic denervation.
D000613:Aminobutyrates / Q000378:metabolism*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006892:Hydroxydopamines / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D011955:Receptors, Drug / Q000032:analysis* / Q000187:drug effects; D013378:Substantia Nigra / Q000378:metabolism; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000613:Aminobutyrates; D006892:Hydroxydopamines; D011759:Pyrrolidines; D011955:Receptors, Drug; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; D007608:Kainic Acid