Increase in Striatal [3H]Muscimol Binding Following Intrastriatal Injection of Kainic Acid: A Denervation Supersensitivity Phenomenon

Abstract

The effect of intrastriatal microinjection of kainic acid (KA) on specific binding of [3H]muscimol to the particulate fractions obtained from rat corpus striatum (CS), globus pallidus (GP), substantia nigra (SN) and cerebral cortex (CC) was examined. Seven days after the unilateral intrastriatal microinjection of KA, the amount of specifically bound [3H]muscimol was significantly increased at the injected site; no significant alteration of [3H]muscimol binding was found in GP, SN or CC. Scatchard analysis of striatal binding revealed that microinjection of KA significantly increased the affinity (KD of GABA receptors on the injected (lesioned) side of the CS without affecting the total number of binding sites (Bmax). This significant increase in [3H]muscimol binding was eliminated by pretreating particulate fractions from the CS with Triton X-100, a non-ionic detergent. No statistically significant difference in amounts of [3H]muscimol binding was detected when the preparations from the KA-treated and non-treated CS were preincubated with 0.05% Triton X-100, respectively. Scatchard analysis using CS preparations treated with 0.05% Triton X-100 revealed that the affinity of the GABA receptor was increased by treatment with Triton X-100, while Bmax was unchanged by this treatment. Neuronal degeneration produced by KA in vivo and pretreatment of particulate preparations with Triton X-100 in vitro may increase the amount of specifically bound [3H]muscimol to CS preparations by a similar molecular mechanism.