Kainic acid-induced decrease in hippocampal corticosteroid receptors.
The potential role of excitatory amino acids in the regulation of brain corticosteroid receptors was examined using systemic administration of kainic acid. Administration of kainic acid (5, 10, and 15 mg/kg) to 24-h adrenalectomized rats that were killed 3 h later produced large, dose-related decreases in glucocorticoid receptors (GR) in hippocampus (23-63%), frontal cortex (22-76%), and striatum (41-49%). Kainic acid did not decrease hypothalamic GR. Hippocampal mineralocorticoid receptors (MR) were also markedly decreased (50-71%) by kainic acid. Significant decreases in corticosteroid receptors could be detected as soon as 1 h after kainic acid (10 mg/kg) administration. Decreases in hippocampal, cortical, and hypothalamic GR as well as hippocampal MR were observed 24 h after administration of kainic acid (10 mg/kg) to adrenalectomized rats. Kainic acid (10 mg/kg) also significantly decreased hippocampal GR and MR as well as GR in the other three brain regions when administered to adrenal-intact rats that were subsequently adrenalectomized and killed 48 h after drug administration. The kainic acid-induced decreases in hippocampal GR and MR binding were due to decreases in the maximum number of binding sites (Bmax) with no change in the apparent affinity (KD). Kainic acid when added in vitro did not displace the GR and MR radioligands from their respective receptors. These studies demonstrate that excitatory amino acids play a prominent role in the regulation of hippocampal corticosteroid receptors. In addition, the data indicate that noncorticosterone factors are involved in corticosteroid receptor plasticity.
Lowy
M T
MT
Department of Psychiatry, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106.
D000315:Adrenalectomy; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000378:metabolism*; D007608:Kainic Acid / Q000494:pharmacology*; D008297:Male; D008901:Mineralocorticoids / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D018161:Receptors, Mineralocorticoid; D011987:Receptors, Steroid / Q000378:metabolism
D008901:Mineralocorticoids; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D011987:Receptors, Steroid; D007608:Kainic Acid