The escalation in ethanol consumption following chronic intermittent ethanol exposure is blunted in mice expressing ethanol-resistant GluN1 or GluN2A NMDA receptor subunits
| Autor: | Dominic A. Gioia, John J. Woodward, Gregg E. Homanics, Marcelo F. Lopez, Paula A. Zamudio |
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| Rok vydání: | 2020 |
| Předmět: |
Male
medicine.medical_specialty Alcohol Drinking Glutamic Acid Nerve Tissue Proteins Receptors N-Methyl-D-Aspartate Article Mice 03 medical and health sciences Glutamatergic chemistry.chemical_compound 0302 clinical medicine Internal medicine medicine Animals Receptor Pharmacology Ethanol Dose-Response Relationship Drug Chemistry Alcohol dependence Glutamate receptor Brain Ethanol exposure Chronic alcohol 030227 psychiatry Alcoholism Endocrinology NMDA receptor Female 030217 neurology & neurosurgery |
| Zdroj: | Psychopharmacology (Berl) |
| ISSN: | 1432-2072 0033-3158 |
| DOI: | 10.1007/s00213-020-05680-z |
| Popis: | N-methyl-D-aspartate receptors (NMDARs) are glutamate-gated ion channels essential for glutamatergic transmission and plasticity. NMDARs are inhibited by acute ethanol and undergo brain region specific adaptations after chronic alcohol exposure. In previous studies, we reported that knock-in mice expressing ethanol-insensitive GluN1 or GluN2A NMDAR subunits display altered behavioral responses to acute ethanol and genotype-dependent changes in drinking using protocols that do not produce dependence. A key unanswered question is whether the intrinsic ethanol sensitivity of NMDARs also plays a role in determining behavioral adaptations that accompany the development of dependence. To test this, we exposed mice to repeated cycles of chronic intermittent ethanol (CIE) vapor known to produce a robust escalation in ethanol consumption and preference. As expected, wild-type mice showed a significant increase from baseline in ethanol consumption and preference after each of the four weekly CIE cycles. In contrast, ethanol consumption in male GluN2A(A825W) mice was unchanged following cycles 1, 2 and 4 cycles of CIE with a modest increase appearing after cycle 3. Wild-type and GluN2A(A825W) female mice did not show a clear or consistent escalation in ethanol consumption or preference following CIE treatment. In male GluN1(F639A) mice, the increase in ethanol consumption observed with their wild-type littermates was delayed until later cycles of exposure. These results suggest that the acute ethanol sensitivity of NMDARs especially those containing the GluN2A subunit may be a critical factor in the in the escalation of ethanol intake in alcohol dependence. |
| Databáze: | OpenAIRE |
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