title: Reserpine attenuates D-amphetamine and MDMA-induced transmitter release in vivo: a consideration of dose, core temperature and dopamine synthesis.
abstract: 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.
authors.affiliation: University of Mississippi, Department of Psychology, 301 Peabody Bldg., University, MS 38677, USA.
authors.forename: K E
authors.initials: KE
authors.lastname: Sabol
authors.forename: L S
authors.initials: LS
authors.lastname: Seiden
mesh_terms: D000818:Animals; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D003913:Dextroamphetamine / Q000494:pharmacology*; D004298:Dopamine / Q000096:biosynthesis; D015259:Dopamine Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012110:Reserpine / Q000494:pharmacology*; D018490:Serotonin Agents / Q000494:pharmacology
chemical_list: D015259:Dopamine Agents; D018377:Neurotransmitter Agents; D018490:Serotonin Agents; D012110:Reserpine; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D003913:Dextroamphetamine; D004298:Dopamine