Prefrontal glutamate correlates of methamphetamine sensitization and preference
Autor: | Lisa M. Schwartz, Ganesh Rajasekar, Katherine O. Travis, John J. Holloway, Lawrence E. Urman, Tod E. Kippin, Rianne R. Campbell, Paige N. Ruiz, Hannah M. Barrett, Melissa G. Wroten, Bailey W. Miller, Dan Maliniak, Tamara J. Phillips, Courtney L. McKenna, Kevin D. Lominac, Sema G. Quadir, Andrew B. Thompson, Karen K. Szumlinski |
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Přispěvatelé: | Dalley, Jeffrey |
Rok vydání: | 2015 |
Předmět: |
0301 basic medicine
Male Receptor expression Amino Acid Transport System X-AG Conditioning Classical Self Administration Inbred C57BL Synaptic Transmission Methamphetamine Mice 0302 clinical medicine Homer Scaffolding Proteins Receptors AMPA 2.1 Biological and endogenous factors Psychology Aetiology Central Nervous System Sensitization Chemistry General Neuroscience Glutamate receptor Substance Abuse pre-frontal cortex Phenotype NMDA receptor Cognitive Sciences medicine.drug N-Methyl-D-Aspartate medicine.medical_specialty Drug Abuse (NIDA Only) Glutamic Acid Prefrontal Cortex addiction vulnerability Basic Behavioral and Social Science Receptors N-Methyl-D-Aspartate Article 03 medical and health sciences Glutamatergic Internal medicine Behavioral and Social Science medicine Genetics Animals metabotropic glutamate receptor Receptors AMPA Neurology & Neurosurgery Neurosciences Glutamic acid Homer proteins Classical Brain Disorders Mice Inbred C57BL 030104 developmental biology Endocrinology Metabotropic receptor Metabotropic glutamate receptor Central Nervous System Stimulants Neuroscience 030217 neurology & neurosurgery Conditioning |
Zdroj: | The European journal of neuroscience, vol 43, iss 5 Lominac, KD; Quadir, SG; Barrett, HM; McKenna, CL; Schwartz, LM; Ruiz, PN; et al.(2016). Prefrontal glutamate correlates of methamphetamine sensitization and preference. EUROPEAN JOURNAL OF NEUROSCIENCE, 43(5), 689-702. doi: 10.1111/ejn.13159. UC Santa Barbara: Retrieved from: http://www.escholarship.org/uc/item/71j334x8 |
ISSN: | 1460-9568 |
Popis: | Methamphetamine (MA) is a widely abused, highly addictive, psychostimulant that elicits pronounced deficits in neurocognitive function related to hypo-functioning of the prefrontal cortex (PFC). Our understanding of how repeated methamphetamine impacts excitatory glutamatergic transmission within the PFC is limited, as is information about the relation between PFC glutamate and addiction vulnerability/resiliency. In vivo microdialysis and immunoblotting studies characterized the effects of methamphetamine (10 injections of 2 mg/kg, IP) upon extracellular glutamate in C57BL/6J mice and upon glutamate receptor and transporter expression, within the medial PFC. Glutamatergic correlates of both genetic and idiopathic variance in MA preference/intake were determined through studies of high versus low MA-drinking selectively bred mouse lines (MAHDR versus MALDR, respectively) and inbred C57BL/6J mice exhibiting spontaneously divergent place-conditioning phenotypes. Repeated methamphetamine sensitized drug-induced glutamate release and lowered indices of NMDA receptor expression in C57BL/6J mice, but did not alter basal extracellular glutamate content or total protein expression of Homer proteins, or metabotropic or AMPA glutamate receptors. Elevated basal glutamate, blunted methamphetamine-induced glutamate release and ERK activation, as well as reduced protein expression of mGlu2/3 and Homer2a/b were all correlated biochemical traits of selection for high versus low methamphetamine drinking, and Homer2a/b levels were inversely correlated with the motivational valence of methamphetamine in C57BL/6J mice. These data provide novel evidence that repeated, low-dose, methamphetamine is sufficient to perturb pre- and post-synaptic aspects of glutamate transmission within the medial PFC and that glutamate anomalies within this region may contribute to both genetic and idiopathic variance in methamphetamine addiction vulnerability/resiliency. |
Databáze: | OpenAIRE |
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