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Methamphetamine induces alterations on hippocampal NMDA and AMPA receptor subunit levels and impairs spatial working memory

Simões, P.F ; Silva, A.P ; Pereira, F.C ; Marques, E ; Grade, S ; Milhazes, N ; Borges, F ; Ribeiro, C.F ; Macedo, T.R

Neuroscience, 2007-12, Vol.150 (2), p.433-441 [Periódico revisado por pares]

Oxford: Elsevier Ltd

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Título:
Methamphetamine induces alterations on hippocampal NMDA and AMPA receptor subunit levels and impairs spatial working memory
Autor: Simões, P.F ; Silva, A.P ; Pereira, F.C ; Marques, E ; Grade, S ; Milhazes, N ; Borges, F ; Ribeiro, C.F ; Macedo, T.R
Assuntos: Animals ; astrogliosis ; Biological and medical sciences ; Central Nervous System Stimulants - pharmacology ; Fluoresceins ; Fundamental and applied biological sciences. Psychology ; Gliosis - chemically induced ; Gliosis - metabolism ; Gliosis - physiopathology ; GluR2 ; Glutamic Acid - metabolism ; Hippocampus - drug effects ; Hippocampus - metabolism ; Hippocampus - physiopathology ; Male ; Maze Learning - drug effects ; Maze Learning - physiology ; Medical sciences ; Memory Disorders - chemically induced ; Memory Disorders - metabolism ; Memory Disorders - physiopathology ; Memory, Short-Term - drug effects ; Memory, Short-Term - physiology ; Methamphetamine - pharmacology ; Nerve Degeneration - chemically induced ; Nerve Degeneration - metabolism ; Nerve Degeneration - physiopathology ; Neurology ; Neuropharmacology ; NR1 ; NR2A ; Organic Chemicals ; Pharmacology. Drug treatments ; Protein Subunits - drug effects ; Protein Subunits - metabolism ; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer ; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease) ; Psychology. Psychoanalysis. Psychiatry ; Psychopharmacology ; psychostimulants ; Rats ; Rats, Sprague-Dawley ; Receptors, AMPA - drug effects ; Receptors, AMPA - metabolism ; Receptors, N-Methyl-D-Aspartate - drug effects ; Receptors, N-Methyl-D-Aspartate - metabolism ; Synaptic Transmission - drug effects ; Synaptic Transmission - physiology ; Up-Regulation - drug effects ; Up-Regulation - physiology ; Vertebrates: nervous system and sense organs
É parte de: Neuroscience, 2007-12, Vol.150 (2), p.433-441
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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Descrição: Abstract Methamphetamine (METH) is a powerful psychostimulant that increases glutamate (Glu) levels in the mammalian brain and it is currently known that hippocampi are particularly susceptible to METH. Moreover, it is well established that the overactivation of N -methyl- d -aspartate (NMDA) and AMPA ionotropic Glu receptors causes excitotoxicity. In the present study, we investigated the effect of acute (30 mg/kg) versus escalating dose (ED) administration of METH on NMDA receptor 1, NMDA receptor 2 and glutamate receptor 2 (GluR2) subunit expression in the hippocampus and on memory. Adult Sprague–Dawley rats were injected s.c. during six consecutive days with saline (control and acute groups) or with a growing dose of METH (10, 15, 15, 20, 20, 25 mg/kg/day; ED group). On the 7th day, both METH groups were injected with a ‘bolus’ of 30 mg/kg METH whereas controls received saline. Western blot analysis showed an increase of GluR2 and NR2A expression levels and no alterations on NR1 subunit in the acute group. On the other hand, in the ED group, GluR2 and NR2A expression levels were unaltered and there was a decrease on NR1 levels. Moreover, we did not observe neurodegeneration with both administration paradigms, as assessed by Fluoro-Jade C staining, but we did observe a strong astrogliosis in the acute administration group by using both immunohistochemistry and Western blot analysis. The impact of METH on working memory was evaluated using the Y maze test and revealed significant mnemonic deficit in the rats acutely treated with the drug. Overall, our results suggest a protection mechanism under conditions of METH administration by decreasing permeability and/or functionality of NMDA and AMPA receptors, which has implications on memory. So, the participation of the glutamatergic system should be considered as an important pharmacological target to design new strategies to prevent or diminish the harmful effect of drug consumption.
Editor: Oxford: Elsevier Ltd
Idioma: Inglês

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Methamphetamine induces alterations on hippocampal NMDA and AMPA receptor subunit levels and impairs spatial working memory

Simões, P.F ; Silva, A.P ; Pereira, F.C ; Marques, E ; Grade, S ; Milhazes, N ; Borges, F ; Ribeiro, C.F ; Macedo, T.R

Oxford: Elsevier Ltd

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