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 7th 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.
Highlights
Many studies have focused on the implication of the serotonin and dopamine systems in neuroadaptive responses to the recreational drug 3,4-methylenedioxy-metamphetamine (MDMA)
For each brain region 7 house-keeping genes (HKG) were run by qPCR
The effects of repeated intermittent MDMA administration, 3 × 1 mg/kg (MDMA low) or 3 × 5 mg/kg (MDMA high), every 7th day for 4 weeks are presented as relative mRNA expressions in percent of the relative cycle numbers for controls, Figure 1 and 2
Summary
Many studies have focused on the implication of the serotonin and dopamine systems in neuroadaptive responses to the recreational drug 3,4-methylenedioxy-metamphetamine (MDMA). Many studies have focused on neuroadaptive responses in the serotonin and dopamine systems towards MDMA [8,9]. The major excitatory neurotransmitter in the CNS is the glutamate system [10] It is interactive with GABA, dopamine and serotonin, especially through the regulation of the corticofugal neuronal activity between the forebrain cortex and subcortical brain regions [11,12,13,14,15]. Microiontophoretic application of MDMA has been shown to inhibit glutamate evoked firing of most cells in the nucleus accumbens [20], possibly through the drug mediated release of dopamine and serotonin [21]. Knowledge of glutamatergic gene-transcript regulation following MDMA administration is limited
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
