Methamphetamine Addiction Vulnerability: The Glutamate, the Bad, and the Ugly
| Autor: | Elissa K. Fultz, Kevin D. Lominac, Matthias Klugmann, Georg von Jonquieres, Matan Cohen, Sema G. Quadir, Tamara J. Phillips, Bailey W. Miller, Rianne R. Campbell, Andrew B. Thompson, Tod E. Kippin, Karen K. Szumlinski, Douglas L. Martin, Chelsea N. Brown |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Microdialysis Inbred Strains Self Administration Receptors Metabotropic Glutamate Medical and Health Sciences Nucleus Accumbens Developmental psychology Methamphetamine Mice Substance Misuse 0302 clinical medicine Homer Scaffolding Proteins Receptors Metabotropic Glutamate Addictive 2.1 Biological and endogenous factors Aetiology Psychiatry High prevalence Glutamate receptor Biological Sciences Metabotropic Glutamate 5 Conditioned place preference Substance Withdrawal Syndrome Gene Knockdown Techniques Disease Susceptibility Glutamate Homer Proteins Self-administration Psychology Addiction vulnerability medicine.drug Receptor medicine.medical_specialty Receptor Metabotropic Glutamate 5 Glutamic Acid Mice Inbred Strains macromolecular substances Article MAHDR 03 medical and health sciences medicine Humans Animals Biological Psychiatry Behavior Metabotropic glutamate receptor Psychology and Cognitive Sciences NMDA receptor Homer proteins Brain Disorders Behavior Addictive 030104 developmental biology Good Health and Well Being Etiology Central Nervous System Stimulants Drug Abuse (NIDA only) 030217 neurology & neurosurgery |
| Zdroj: | Biological psychiatry, vol 81, iss 11 |
| Popis: | BackgroundThe high prevalence and severity of methamphetamine (MA) abuse demands greater neurobiological understanding of its etiology.MethodsWe conducted immunoblotting and in vivo microdialysis procedures in MA high/low drinking mice, as well as in isogenic C57BL/6J mice that varied in their MA preference/taking, to examine the glutamate underpinnings of MA abuse vulnerability. Neuropharmacological and Homer2 knockdown approaches were also used in C57BL/6J mice to confirm the role for nucleus accumbens (NAC) glutamate/Homer2 expression in MA preference/aversion.ResultsWe identified a hyperglutamatergic state within the NAC as a biochemical trait corresponding with both genetic and idiopathic vulnerability for high MA preference and taking. We also confirmed that subchronic subtoxic MA experience elicits a hyperglutamatergic state within the NAC during protracted withdrawal, characterized by elevated metabotropic glutamate 1/5 receptor function and Homer2 receptor-scaffolding protein expression. A high MA-preferring phenotype was recapitulated by elevating endogenous glutamate within the NAC shell of mice and we reversed MA preference/taking by lowering endogenous glutamate and/or Homer2 expression within this subregion.ConclusionsOur data point to an idiopathic, genetic, or drug-induced hyperglutamatergic state within the NAC as a mediator of MA addiction vulnerability. |
| Databáze: | OpenAIRE |
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