Extensive neuroadaptive changes in cortical gene-transcript expressions of the glutamate system in response to repeated intermittent MDMA administration in adolescent ratsReportar como inadecuado




Extensive neuroadaptive changes in cortical gene-transcript expressions of the glutamate system in response to repeated intermittent MDMA administration in adolescent rats - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

BMC Neuroscience

, 9:39

First Online: 17 April 2008Received: 18 December 2007Accepted: 17 April 2008

Abstract

BackgroundMany studies have focused on the implication of the serotonin and dopamine systems in neuroadaptive responses to the recreational drug 3,4-methylenedioxy-metamphetamine MDMA. Less attention has been given to the major excitatory neurotransmitter glutamate known to be implicated in schizophrenia and drug addiction. The aim of the present study was to investigate the effect of repeated intermittent MDMA administration upon gene-transcript expression of the glutamate transporters EAAT1, EAAT2-1, EAAT2-2, the glutamate receptor subunits of AMPA GluR1, GluR2, GluR3, the glutamate receptor subunits of NMDA NR1, NR2A and NR2B, as well as metabotropic glutamate receptors mGluR1, mGluR2, mGluR3, mGluR5 in six different brain regions. Adolescent male Sprague Dawley rats received MDMA at the doses of 3 × 1 and 3 × 5 mg-kg-day, or 3× vehicle 3 hours apart, every 7 day for 4 weeks. The gene-transcript levels were assessed using real-time PCR validated with a range of housekeeping genes.

ResultsThe findings showed pronounced enhancements in gene-transcript expression of GluR2, mGluR1, mGluR5, NR1, NR2A, NR2B, EAAT1, and EAAT2-2 in the cortex at bregma +1.6. In the caudate putamen, mRNA levels of GluR3, NR2A, and NR2B receptor subunits were significantly increased. In contrast, the gene-transcript expression of GluR1 was reduced in the hippocampus. In the hypothalamus, there was a significant increase of GluR1, GluR3, mGluR1, and mGluR3 gene-transcript expressions.

ConclusionRepeated intermittent MDMA administration induces neuroadaptive changes in gene-transcript expressions of glutamatergic NMDA and AMPA receptor subunits, metabotropic receptors and transporters in regions of the brain regulating reward-related associative learning, cognition, and memory and neuro-endocrine functions.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2202-9-39 contains supplementary material, which is available to authorized users.

Download fulltext PDF



Autor: Anna MS Kindlundh-Högberg - Anna Blomqvist - Rana Malki - Helgi B Schiöth

Fuente: https://link.springer.com/







Documentos relacionados