PMID- 9739110 OWN - NLM STAT- MEDLINE DCOM- 19981120 LR - 20190614 IS - 0006-8993 (Print) IS - 0006-8993 (Linking) VI - 806 IP - 1 DP - 1998 Sep 21 TI - Reserpine attenuates D-amphetamine and MDMA-induced transmitter release in vivo: a consideration of dose, core temperature and dopamine synthesis. PG - 69-78 AB - Amphetamine releases dopamine through a transporter-mediated mechanism. The purpose of this report was to further our understanding of the intracellular pool from which amphetamine releases dopamine: the cytoplasmic pool, the vesicular pool, or both. Rats were treated with D-amphetamine (AMPH) (1.0 or 10.0 mg/kg) or an amphetamine analog, methylenedioxymethamphetamine (MDMA) (2.0, 5.0, or 10.0 mg/kg). Pre-treatment with 10.0 mg/kg reserpine (18 h prior to AMPH or MDMA) attenuated dopamine release for high and low AMPH doses; however the low-dose effect showed borderline significance. Pre-treatment with 10.0 mg/kg reserpine attenuated dopamine and serotonin release induced by MDMA. The dopamine effect was seen at all three MDMA doses; the effect on serotonin was only measured at the 10.0 mg/kg dose. Reserpine pre-treatment caused reductions in core body temperature; heating the rats to normal body temperature for 3 h prior to AMPH or MDMA, and during the 4 h post-treatment period partially reversed the reserpine-induced attenuation of dopamine release. However, the intermediate level of dopamine release for the reserpinized-heated animals was not significantly different from either the reserpine group (not heated) or the AMPH or MDMA alone groups. In a separate group of rats, the effects of reserpine and reserpine+heat on dopamine synthesis were measured. DOPA accumulation after treatment with the aromatic acid decarboxylase inhibitor NSD-1015 (100 mg/kg, 30 min before sacrifice), was greater in rats treated with reserpine compared to controls; heating the reserpinized rats did not significantly alter the amount of DOPA accumulation; however there was a trend towards further increase. These results suggest that D-amphetamine releases dopamine that is stored in both vesicles and the cytoplasm. Cooling may contribute to the attenuation of AMPH or MDMA-induced dopamine release observed after reserpine; however, AMPH or MDMA dependence upon vesicular stores most likely explains the diminished release after reserpine. The attenuation of AMPH or MDMA-induced transmitter release by reserpine is thought to be counteracted by a reserpine-induced replenishment of stores. Therefore, all doses of D-amphetamine may use vesicular stores; the degree to which new synthesis counteracts the vesicular depletion may be the variable which differentiates low from high doses of D-amphetamine. CI - Copyright 1998 Elsevier Science B.V. FAU - Sabol, K E AU - Sabol KE AD - University of Mississippi, Department of Psychology, 301 Peabody Bldg., University, MS 38677, USA. FAU - Seiden, L S AU - Seiden LS LA - eng GR - DA00085/DA/NIDA NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - Netherlands TA - Brain Res JT - Brain research JID - 0045503 RN - 0 (Dopamine Agents) RN - 0 (Neurotransmitter Agents) RN - 0 (Serotonin Agents) RN - 8B1QWR724A (Reserpine) RN - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine) RN - TZ47U051FI (Dextroamphetamine) RN - VTD58H1Z2X (Dopamine) SB - IM MH - Animals MH - Body Temperature/drug effects/physiology MH - Dextroamphetamine/*pharmacology MH - Dopamine/biosynthesis MH - Dopamine Agents/*pharmacology MH - Dose-Response Relationship, Drug MH - Male MH - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology MH - Neurotransmitter Agents/*metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Reserpine/*pharmacology MH - Serotonin Agents/pharmacology EDAT- 1998/09/18 00:00 MHDA- 1998/09/18 00:01 CRDT- 1998/09/18 00:00 PHST- 1998/09/18 00:00 [pubmed] PHST- 1998/09/18 00:01 [medline] PHST- 1998/09/18 00:00 [entrez] AID - S0006-8993(98)00720-3 [pii] AID - 10.1016/s0006-8993(98)00720-3 [doi] PST - ppublish SO - Brain Res. 1998 Sep 21;806(1):69-78. doi: 10.1016/s0006-8993(98)00720-3.