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- Title
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
- Authors
Acquas, Elio; Pisanu, Augusta; Spiga, Saturnino; Plumitallo, Antonio; Zernig, Gerald; di Chiara, Gaetano
- 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 D1 receptor antagonist, SCH 39166, prevented the increase in pERK elicited by R,S(±)-MDMA and S(+)-MDMA, while the D2/3 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 D1-dependent DA transmission.
- Subjects
ECSTASY (Drug); DOPAMINE; ENANTIOMERS; PHOSPHORYLATION; CELL nuclei; RATS
- Publication
Journal of Neurochemistry, 2007, Vol 102, Issue 1, p121
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1111/j.1471-4159.2007.04451.x