Binge alcohol drinking by mice requires intact group 1 metabotropic glutamate receptor signaling within the central nucleus of the amygdala
| Autor: | Cozzoli, Debra K, Courson, Justin, Wroten, Melissa G, Greentree, Daniel I, Lum, Emily N, Campbell, Rianne R, Thompson, Andrew B, Maliniak, Dan, Worley, Paul F, Jonquieres, Georg, Klugmann, Matthias, Finn, Deborah A, Szumlinski, Karen K |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Knockout glutamate 129 Strain Underage Drinking Inbred C57BL Cardiovascular Medical and Health Sciences Oral and gastrointestinal Binge Drinking Mice Substance Misuse Alcohol Use and Health Homer Scaffolding Proteins Receptors Behavioral and Social Science Metabotropic Glutamate Animals metabotropic glutamate receptor phospholipase C Cancer Pediatric Psychiatry Psychology and Cognitive Sciences Neurosciences Amygdala Brain Disorders Stroke Alcoholism Good Health and Well Being Homer central nucleus of the amygdala Carrier Proteins Signal Transduction |
| Zdroj: | Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, vol 39, iss 2 |
| Popis: | Despite the fact that binge alcohol drinking (intake resulting in blood alcohol concentrations (BACs) 80 mg% within a 2-h period) is the most prevalent form of alcohol-use disorders (AUD), a large knowledge gap exists regarding how this form of AUD influences neural circuits mediating alcohol reinforcement. The present study employed integrative approaches to examine the functional relevance of binge drinking-induced changes in glutamate receptors, their associated scaffolding proteins and certain signaling molecules within the central nucleus of the amygdala (CeA). A 30-day history of binge alcohol drinking (for example, 4-5 g kg(-1) per 2 h(-1)) elevated CeA levels of mGluR1, GluN2B, Homer2a/b and phospholipase C (PLC) β3, without significantly altering protein expression within the adjacent basolateral amygdala. An intra-CeA infusion of mGluR1, mGluR5 and PLC inhibitors all dose-dependently reduced binge intake, without influencing sucrose drinking. The effects of co-infusing mGluR1 and PLC inhibitors were additive, whereas those of coinhibiting mGluR5 and PLC were not, indicating that the efficacy of mGluR1 blockade to lower binge intake involves a pathway independent of PLC activation. The efficacy of mGluR1, mGluR5 and PLC inhibitors to reduce binge intake depended upon intact Homer2 expression as revealed through neuropharmacological studies of Homer2 null mutant mice. Collectively, these data indicate binge alcohol-induced increases in Group1 mGluR signaling within the CeA as a neuroadaptation maintaining excessive alcohol intake, which may contribute to the propensity to binge drink. |
| Databáze: | OpenAIRE |
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