Correlation between 5-HT content and uptake site density following (S)-MDMA and dexfenfluramine-induced depletion, and with neuroprotection by the glycine site-specific NMDA antagonist ACEA 1021.
3,4-Methylenedioxymethamphetamine (MDMA) and fenfluramine are amphetamine analogues that both cause long-term depletion of serotonin (5-HT) and 5-HT uptake sites in brain tissue. Depletion caused by these amphetamines is commonly measured by labeling 5-HT uptake sites using 3H-paroxetine combined with autoradiography or, alternatively measuring the concentration of 5-HT in tissue using high-performance liquid chromatography (HPLC). A close correlation between the 5-HT concentration measured in micropunch samples and the density of 3H-paroxetine-labeled 5-HT uptake sites measured in corresponding 20 micron coronal slices was determined (R2 = 0.92). These methods combined demonstrated that the glycine-site specific NMDA antagonist ACEA 1021 (4 x 30 mg/kg, i.p., 2 hourly) given 30 minutes before (S)-MDMA (4 x 10 mg/kg, i.p., 2 hourly) was able to prevent the depletion of both 5-HT content and uptake site density but unable to prevent the depletion of 5-HT content and uptake site density caused dexfenfluramine (4 x 15 mg/kg, i.p., 2 hourly).
Russell
B R
BR
Department of Pharmacology, School of Medical Sciences, University of Otago, Dunedin, New Zealand.
Laverty
R
R
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D020372:Dexfenfluramine / Q000494:pharmacology*; D004347:Drug Interactions; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D017374:Paroxetine / Q000493:pharmacokinetics; D011810:Quinoxalines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism* / Q000493:pharmacokinetics; D018490:Serotonin Agents / Q000494:pharmacology*; D014316:Tritium / Q000493:pharmacokinetics
D018696:Neuroprotective Agents; D011810:Quinoxalines; D018490:Serotonin Agents; D014316:Tritium; D012701:Serotonin; C092062:licostinel; D017374:Paroxetine; D020372:Dexfenfluramine; D018817:N-Methyl-3,4-methylenedioxyamphetamine