Differential effects of intravenous R,S‐(±)‐3,4‐methylenedioxymethamphetamine (MDMA, Ecstasy) and its S(+)‐ and R(−)‐enantiomers on dopamine transmission and extracellular signal regulated kinase phosphorylation (pERK) in the rat nucleus accumbens shell and core
Elio Acquas, Augusta Pisanu, Saturnino Spiga, Antonio Plumitallo, Gerald Zernig, Gaetano Di Chiara
Journal of Neurochemistry January 22, 2007 DOI: 10.1111/j.1471-4159.2007.04451.x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Male Sprague–Dawley rats |
| Interventions | R SCH 39166 raclopride |
| Dose | R,S(±)-MDMA: 0.64, 1, and 2 mg/kg i.v.; S(+)-MDMA: doses not specified; R(−)-MDMA: 1 and 2 mg/kg i.v.; SCH 39166 and raclopride: doses not specified |
| Measures | extracellular dopamine (microdialysis with HPLC), ERK phosphorylation (density/neuron and number of pERK-positive neurons/area) |
| Topics | MDMA |
| Keywords | Microdialysis Pharmacology Nucleus accumbens Mesolimbic pathway Dopaminergic |
| Citations | 52 |
| Key findings | The S(+)-MDMA enantiomer accounts for the dopamine stimulant effects of racemic MDMA, and pERK in the nucleus accumbens shell and core represents a post-synaptic correlate of D1-dependent dopamine transmission. |
Abstract
Abstract R,S(±)‐3,4‐methylenedioxymethamphetamine (R,S(±)‐MDMA, ‘Ecstasy’) is known to stimulate dopamine (DA) transmission in the nucleus accumbens (NAc). In order to investigate the post‐synaptic correlates of pre‐synaptic changes in DA transmission and their relationship with MDMA enantiomers, we studied the effects of R,S(±)‐MDMA, S(+)‐MDMA, and R(−)‐MDMA on extracellular DA and phosphorylated extracellular signal regulated kinase (pERK) in the NAc shell and core. Male Sprague–Dawley rats, implanted with a catheter in the femoral vein and vertical concentric dialysis probes in the NAc shell and core, were administered i.v. saline, R,S(±)‐MDMA, S(+)‐MDMA, or R(−)‐MDMA. Extracellular DA was monitored by in vivo microdialysis with HPLC. Intravenous R,S(±)‐MDMA (0.64, 1, and 2 mg/kg) increased dialysate DA, preferentially in the shell, in a dose‐related manner. S(+)‐MDMA exerted similar effects but at lower doses than R,S(±)‐MDMA, while R(−)‐MDMA (1 and 2 mg/kg) failed to affect dialysate DA. R,S(±)‐ and S(+)‐MDMA but not R(−)‐MDMA increased ERK phosphorylation (expressed as density/neuron and number of pERK‐positive neurons/area) in both subdivisions of the NAc. The administration of the D 1 receptor antagonist, SCH 39166, prevented the increase in pERK elicited by R,S(±)‐MDMA and S(+)‐MDMA, while the D 2/3 receptor antagonist, raclopride, increased pERK in the NAc core per se but failed to affect the R,S(±)‐MDMA‐elicited stimulation of pERK. The present results provide evidence that the DA stimulant effects of racemic MDMA are accounted for by the S(+)‐enantiomer and that pERK may represent a post‐synaptic correlate of the stimulant effect of R,S(±)‐MDMA on D 1 ‐dependent DA transmission.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 17
- Persistent MDMA‐induced dopaminergic neurotoxicity in the striatum and substantia nigra of mice Journal of Neurochemistry September 24, 2008
- Dark Classics in Chemical Neuroscience: 3,4-Methylenedioxymethamphetamine ACS Chemical Neuroscience July 12, 2018
- Role of Serotonin via 5-HT2B Receptors in the Reinforcing Effects of MDMA in Mice PLoS One November 20, 2009
- MPTP‐induced dopamine neuron degeneration and glia activation is potentiated in MDMA‐pretreated mice Movement Disorders September 20, 2013
- Microglial and astroglial activation by 3,4‐methylenedioxymethamphetamine (MDMA) in mice depends on S(+) enantiomer and is associated with an increase in body temperature and motility Journal of Neurochemistry October 20, 2012
and 12 more in the library
Cites 7
- Carrier‐Mediated Release of Serotonin by 3,4‐Methylenedioxymethamphetamine: Implications for Serotonin‐Dopamine Interactions Journal of Neurochemistry 1996
- The pharmacology of the acute hyperthermic response that follows administration of 3,4‐methylenedioxymethamphetamine (MDMA, ‘ecstasy’) to rats British Journal of Pharmacology 2002
- Potentiation of 3,4-methylenedioxymethamphetamine-induced dopamine release and serotonin neurotoxicity by 5-HT2 receptor agonists. European Journal of Pharmacology November 3, 1994
- Importance of ERK activation in behavioral and biochemical effects induced by MDMA in mice British Journal of Pharmacology October 29, 2003
- Reinforcing Effects of MDMA (‘Ecstasy’) in Drug-Naive and Cocaine-Trained Rats Pharmacology 2001
and 2 more in the library