Rapid Communication Chronic Ingestion of Ethanol Up‐Regulates NMDAR1 Receptor Subunit Immunoreactivity in Rat Hippocampus

Journal of Neurochemistry - Tập 62 Số 4 - Trang 1635-1638 - 1994
Louis Trevisan1, Lawrence W. Fitzgerald1, Nils Brose2, Gregory P. Gasic2, Stephen F. Heinemann2, Ronald S. Duman1, Eric J. Nestler1
1Laboratory of Molecular Psychiatry and Departments of Psychiatry and Pharmacology, Yale University School of Medicine, New Haven, Connecticut, U.S.A.
2Molecular Neurobiology Laboratory, The Salk Institute, LaJolla, California, U.S.A.

Tóm tắt

We examined the effects of chronic ethanol exposure on the levels of N‐methyl‐D‐aspartate receptor subunit 1 (NMDAR1) protein, an essential component of N‐methyl‐D‐aspar‐ tate glutamate receptors, in rat brain. By immunoblotting procedures using a specific antibody for the NMDAR1 subunit, we found that ethanol dramatically up‐regulated (by 65%) NMDAR1 immunoreactivity in the hippocampus but not in the nucleus accumbens, cerebral cortex, or striatum. In contrast, ethanol did not alter the levels of glutamate receptor subunit (GLUR) 1 or GLUR2 protein, subunits that make up the α‐amino‐3‐hydroxy‐5‐methy4‐isoxazole propionic acid glutamate receptor, in the hippocampus. Because ethanol can potentially influence many different neurotransmitter systems, we examined whether chronic treatment with several psychotropic drugs with different pharmacological profiles (cocaine, haloperidol, SCH 23390, imipramine, and morphine) could mimic the effect of ethanol. None of these agents increased hippocampal NMDAR1 subunit immunoreactivity after chronic administration. Increased NMDAR1 subunit levels in the hippocampus after chronic ethanol exposure may represent an important neurochemical substrate for some of the features associated with ethanol dependence and withdrawal.

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