Differential effects of chronic ethanol administration and withdrawal on gamma-aminobutyric acid type A and NMDA receptor subunit proteins in male and female rat brain. 2004

Leslie L Devaud, and Paul Alele
Department of Pharmaceutical Sciences, Idaho State University, Pocatello, Idaho 83209-8334, USA. ldevaud@otc.isu.edu

BACKGROUND Investigations have shown that chronic ethanol exposure results in selective alterations in levels of gamma-aminobutyric acid (GABA)A and NMDA receptor subunits. We previously reported significant sex differences in these chronic ethanol-induced adaptations. Because we have more recently found important sex differences in timing for the development of and recovery from ethanol dependence, we wanted to ascertain whether there were associations between overt expression of withdrawal and neuroadaptations at the level of GABAA and NMDA receptors. METHODS Western blot analysis was used to assay protein levels for several GABAA and NMDA receptor subunits in rat cerebral cortex and hippocampus by using subunit-selective antibodies. Rats were fed 6% ethanol in a liquid diet with pair-fed controls. Feeding, harvesting of tissue, and Western blot experiments were all conducted while maintaining the paired design. Tissue was harvested after 3 days of ethanol exposure, 9 days of ethanol exposure, or 3 days of ethanol withdrawal after 14 days of liquid diet administration. RESULTS We again found sex-, subunit-, and brain region-selective effects of ethanol administration and withdrawal for GABAA and NMDA receptors. There was a strong association between increased GABAA receptor alpha4 subunit levels and previously determined withdrawal-induced changes in seizure susceptibility, highlighted by the sex differences in ethanol exposure length required to cause withdrawal signs. In addition, results obtained after 9 days of ethanol administration were in general agreement with previous findings after 14 days of ethanol administration. CONCLUSIONS These data further support the suggestion that alterations in subunit assembly of GABAA and NMDA receptors may have some mechanistic role in neuroadaptations underlying ethanol dependence and withdrawal. Furthermore, significant sex differences in these adaptations suggest that multiple types of adaptations may be elicited, depending on innate differences in the actions/effects of ethanol.

UI MeSH Term Description Entries
D008297 Male Males
D011963 Receptors, GABA-A Cell surface proteins which bind GAMMA-AMINOBUTYRIC ACID and contain an integral membrane chloride channel. Each receptor is assembled as a pentamer from a pool of at least 19 different possible subunits. The receptors belong to a superfamily that share a common CYSTEINE loop. Benzodiazepine-Gaba Receptors,GABA-A Receptors,Receptors, Benzodiazepine,Receptors, Benzodiazepine-GABA,Receptors, Diazepam,Receptors, GABA-Benzodiazepine,Receptors, Muscimol,Benzodiazepine Receptor,Benzodiazepine Receptors,Benzodiazepine-GABA Receptor,Diazepam Receptor,Diazepam Receptors,GABA(A) Receptor,GABA-A Receptor,GABA-A Receptor alpha Subunit,GABA-A Receptor beta Subunit,GABA-A Receptor delta Subunit,GABA-A Receptor epsilon Subunit,GABA-A Receptor gamma Subunit,GABA-A Receptor rho Subunit,GABA-Benzodiazepine Receptor,GABA-Benzodiazepine Receptors,Muscimol Receptor,Muscimol Receptors,delta Subunit, GABA-A Receptor,epsilon Subunit, GABA-A Receptor,gamma-Aminobutyric Acid Subtype A Receptors,Benzodiazepine GABA Receptor,Benzodiazepine Gaba Receptors,GABA A Receptor,GABA A Receptor alpha Subunit,GABA A Receptor beta Subunit,GABA A Receptor delta Subunit,GABA A Receptor epsilon Subunit,GABA A Receptor gamma Subunit,GABA A Receptor rho Subunit,GABA A Receptors,GABA Benzodiazepine Receptor,GABA Benzodiazepine Receptors,Receptor, Benzodiazepine,Receptor, Benzodiazepine-GABA,Receptor, Diazepam,Receptor, GABA-A,Receptor, GABA-Benzodiazepine,Receptor, Muscimol,Receptors, Benzodiazepine GABA,Receptors, GABA A,Receptors, GABA Benzodiazepine,delta Subunit, GABA A Receptor,epsilon Subunit, GABA A Receptor,gamma Aminobutyric Acid Subtype A Receptors
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D005260 Female Females
D000431 Ethanol A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in ALCOHOLIC BEVERAGES. Alcohol, Ethyl,Absolute Alcohol,Grain Alcohol,Alcohol, Absolute,Alcohol, Grain,Ethyl Alcohol
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012727 Sex Characteristics Those characteristics that distinguish one SEX from the other. The primary sex characteristics are the OVARIES and TESTES and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. Gender Characteristics,Gender Differences,Gender Dimorphism,Sex Differences,Sex Dimorphism,Sexual Dichromatism,Sexual Dimorphism,Characteristic, Gender,Characteristic, Sex,Dichromatism, Sexual,Dichromatisms, Sexual,Difference, Sex,Dimorphism, Gender,Dimorphism, Sex,Dimorphism, Sexual,Gender Characteristic,Gender Difference,Gender Dimorphisms,Sex Characteristic,Sex Difference,Sex Dimorphisms,Sexual Dichromatisms,Sexual Dimorphisms
D013375 Substance Withdrawal Syndrome Physiological and psychological symptoms associated with withdrawal from the use of a drug after prolonged administration or habituation. The concept includes withdrawal from smoking or drinking, as well as withdrawal from an administered drug. Drug Withdrawal Symptoms,Withdrawal Symptoms,Drug Withdrawal Symptom,Substance Withdrawal Syndromes,Symptom, Drug Withdrawal,Symptom, Withdrawal,Symptoms, Drug Withdrawal,Symptoms, Withdrawal,Syndrome, Substance Withdrawal,Syndromes, Substance Withdrawal,Withdrawal Symptom,Withdrawal Symptom, Drug,Withdrawal Symptoms, Drug,Withdrawal Syndrome, Substance,Withdrawal Syndromes, Substance
D016194 Receptors, N-Methyl-D-Aspartate A class of ionotropic glutamate receptors characterized by affinity for N-methyl-D-aspartate. NMDA receptors have an allosteric binding site for glycine which must be occupied for the channel to open efficiently and a site within the channel itself to which magnesium ions bind in a voltage-dependent manner. The positive voltage dependence of channel conductance and the high permeability of the conducting channel to calcium ions (as well as to monovalent cations) are important in excitotoxicity and neuronal plasticity. N-Methyl-D-Aspartate Receptor,N-Methyl-D-Aspartate Receptors,NMDA Receptor,NMDA Receptor-Ionophore Complex,NMDA Receptors,Receptors, NMDA,N-Methylaspartate Receptors,Receptors, N-Methylaspartate,N Methyl D Aspartate Receptor,N Methyl D Aspartate Receptors,N Methylaspartate Receptors,NMDA Receptor Ionophore Complex,Receptor, N-Methyl-D-Aspartate,Receptor, NMDA,Receptors, N Methyl D Aspartate,Receptors, N Methylaspartate
D017207 Rats, Sprague-Dawley A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company. Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats

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