Xm. Huang et De. Nichols, 5-HT2 RECEPTOR-MEDIATED POTENTIATION OF DOPAMINE SYNTHESIS AND CENTRAL SEROTONERGIC DEFICITS, European journal of pharmacology, 238(2-3), 1993, pp. 291-296
The hypothesis was tested that serotonin (5-HT) modulates 3,4-methylen
edioxymethamphetamine (MDMA)-induced increase in dopamine synthesis. R
ats were treated with the selective 5-HT2 receptor agonist (R)-1-(2,5-
dimethoxy-4-iodophenyl)-2-aminopropane (R-DOI), the selective serotoni
n releasing agent 5-methoxy-6-methyl-2-aminoindan (MMAI), amphetamine,
MDMA, or a combination of amphetamine and R-DOI or MMAI, followed by
the L-dihydroxyphenylalanine (DOPA) decarboxylase inhibitor 3-hydroxyb
enzylhydrazine (NSD-1015). Rats were killed 45 min after the first inj
ection and striatal DOPA was determined. R-DOI, MMAI, or amphetamine a
lone did not increase DOPA accumulation. However, combination of amphe
tamine with either MMAI or R-DOI significantly increased DOPA accumula
tion. Multiple doses of the R-DOI and amphetamine combination did not
decrease [H-3]paroxetine binding sites at one week after killing. The
results indicate that the dopamine synthesis increasing effect of MDMA
depends both on 5-HT2 receptor stimulation and dopamine efflux.