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
Journal of Neurochemistry – January 22, 2007
Source: OpenAlex
Summary
MDMA, particularly its S(+) enantiomer, significantly boosts dopamine levels in the nucleus accumbens, with a dose-dependent increase observed at 0.64, 1, and 2 mg/kg in male Sprague-Dawley rats. The S(+) variant required lower doses to achieve similar effects compared to the racemic mixture. Notably, R(−)‐MDMA did not impact dopamine levels. Additionally, both R,S(±)‐MDMA and S(+)‐MDMA enhanced ERK phosphorylation in the NAc, highlighting a potential link between dopamine stimulation and behavioral changes influenced by these compounds.
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.