PMID- 15979209 OWN - NLM STAT- MEDLINE DCOM- 20050908 LR - 20221207 IS - 0197-0186 (Print) IS - 0197-0186 (Linking) VI - 47 IP - 5 DP - 2005 Oct TI - Differences in the in vivo dynamics of neurotransmitter release and serotonin uptake after acute para-methoxyamphetamine and 3,4-methylenedioxymethamphetamine revealed by chronoamperometry. PG - 350-61 AB - Illicit use of p-methoxyamphetamine (PMA) is rapidly increasing. However, little is known about the acute effects of PMA on neurotransmission in vivo. High-speed chronoamperometry was used to monitor neurotransmitter release and clearance in anesthetized rats after local application of PMA or 3,4-methylenedioxymethamphetamine (MDMA). In striatum, PMA caused less neurotransmitter release than MDMA. PMA-evoked release could be partially blocked by pre-treatment with a serotonin (5-HT) reuptake inhibitor, suggesting that evoked 5-HT release contributed to the electrochemical signal and was mediated by the 5-HT transporter (SERT). MDMA-evoked release was not blocked by a SERT inhibitor, suggesting that primarily DA was released. To study the effect of these amphetamines on clearance of 5-HT mediated specifically by the SERT, clearance of exogenously applied 5-HT was measured in the CA3 region of the hippocampus. In contrast to the striatum where 5-HT is cleared by both the SERT and the dopamine transporter (DAT), 5-HT is cleared primarily by the SERT in the CA3 region. This is also a region where neither PMA nor MDMA evoked release of neurotransmitter. The maximal inhibition of 5-HT clearance was greater after PMA than MDMA. These data demonstrate in vivo (1) brain region variability in the ability of PMA and MDMA to evoke release of neurotransmitter; (2) that clearance of 5-HT in the striatum is mediated by both the SERT and the DAT; (3) distinct differences in the amount and nature of neurotransmitter released in the striatum after local application of PMA and MDMA and (4) that PMA is a more efficacious inhibitor of 5-HT clearance in the hippocampus than MDMA. These fundamental differences may account for the more severe adverse reactions seen clinically after PMA, compared to MDMA. FAU - Callaghan, Paul D AU - Callaghan PD AD - Department of Physiology, The University of Texas Health Science Center at San Antonio, San Antonio, 78229-3900, USA. FAU - Irvine, Rodney J AU - Irvine RJ FAU - Daws, Lynette C AU - Daws LC LA - eng GR - MH64489/MH/NIMH NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - Neurochem Int JT - Neurochemistry international JID - 8006959 RN - 0 (Amphetamines) RN - 0 (Neurotransmitter Agents) RN - 0 (Piperazines) RN - 0 (Serotonin Agents) RN - 0 (Serotonin Uptake Inhibitors) RN - 333DO1RDJY (Serotonin) RN - 3J928617DW (Zimeldine) RN - 90X28IKH43 (vanoxerine) RN - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine) RN - OVB8F8P39Q (4-methoxyamphetamine) SB - IM MH - Amphetamines/*pharmacology MH - Animals MH - Calibration MH - Dose-Response Relationship, Drug MH - Electrochemistry MH - Electrodes MH - Male MH - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology MH - Neurotransmitter Agents/*metabolism MH - Oxidation-Reduction MH - Piperazines/pharmacology MH - Rats MH - Rats, Sprague-Dawley MH - Serotonin/*metabolism MH - Serotonin Agents/*pharmacology MH - Selective Serotonin Reuptake Inhibitors/pharmacology MH - Zimeldine/pharmacology EDAT- 2005/06/28 09:00 MHDA- 2005/09/09 09:00 CRDT- 2005/06/28 09:00 PHST- 2004/09/09 00:00 [received] PHST- 2005/01/20 00:00 [revised] PHST- 2005/04/06 00:00 [accepted] PHST- 2005/06/28 09:00 [pubmed] PHST- 2005/09/09 09:00 [medline] PHST- 2005/06/28 09:00 [entrez] AID - S0197-0186(05)00118-X [pii] AID - 10.1016/j.neuint.2005.04.026 [doi] PST - ppublish SO - Neurochem Int. 2005 Oct;47(5):350-61. doi: 10.1016/j.neuint.2005.04.026.