5-HT2 receptor-mediated potentiation of dopamine synthesis and central serotonergic deficits.
The hypothesis was tested that serotonin (5-HT) modulates 3,4-methylenedioxymethamphetamine (MDMA)-induced increase in dopamine synthesis. Rats were treated with the selective 5-HT2 receptor agonist (R)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (R-DOI), the selective serotonin 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-hydroxybenzylhydrazine (NSD-1015). Rats were killed 45 min after the first injection and striatal DOPA was determined. R-DOI, MMAI, or amphetamine alone did not increase DOPA accumulation. However, combination of amphetamine with either MMAI or R-DOI significantly increased DOPA accumulation. Multiple doses of the R-DOI and amphetamine combination did not decrease [3H]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.
Huang
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Department of Pharmacology and Toxicology, Purdue University, School of Pharmacy and Pharmacal Sciences, West Lafayette, IN 47907.
Nichols
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D015104:3,4-Methylenedioxyamphetamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000661:Amphetamine / Q000494:pharmacology; D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004295:Dihydroxyphenylalanine / Q000378:metabolism*; D004298:Dopamine / Q000096:biosynthesis*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D006834:Hydrazines / Q000494:pharmacology; D007189:Indans / Q000494:pharmacology; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D000662:Amphetamines; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D006834:Hydrazines; D007189:Indans; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C068879:5-methoxy-6-methyl-2-aminoindan; D012701:Serotonin; D015104:3,4-Methylenedioxyamphetamine; D004295:Dihydroxyphenylalanine; C004297:3-hydroxybenzylhydrazine; D000661:Amphetamine; D018817:N-Methyl-3,4-methylenedioxyamphetamine; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; D004298:Dopamine