RESERPINE ATTENUATES D-AMPHETAMINE AND MDMA-INDUCED TRANSMITTER RELEASE IN-VIVO - A CONSIDERATION OF DOSE, CORE TEMPERATURE AND DOPAMINE SYNTHESIS

Amphetamine releases dopamine through a transporter-mediated mechanism . The purpose of this report was to further our understanding of the i ntracellular pool from which amphetamine releases dopamine: the cytopl asmic pool, the vesicular pool, or both. Rats were treated with D-amph etamine (AMPH) (1.0 or 10.0 mg/kg) or an amphetamine analog, methylene dioxymethamphetamine (MDMA) (2.0, 5.0, or 10.0 mg/kg). Pre-treatment w ith 10.0 mg/kg reserpine (18 h prior to AMPH or MDMA) attenuated dopam ine release for high and low AMPH doses; however the low-dose effect s howed borderline significance. Pre-treatment with 10.0 mg/kg reserpine attenuated dopamine and serotonin release induced by MDMA. The dopami ne effect was seen at all three MDMA doses; the effect on serotonin wa s 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-tre atment 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 fr om either the reserpine group (not heated) or the AMPH or MDMA alone g roups. In a separate group of rats, the effects of reserpine and reser pine + heat on dopamine synthesis were measured. DOPA accumulation aft er 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-amphet amine releases dopamine that is stored in both vesicles and the cytopl asm. Cooling may contribute to the attenuation of AMPH or MDMA-induced dopamine release observed after reserpine; however, AMPH or MDMA depe ndence upon vesicular stores most likely explains the diminished relea se after reserpine. The attenuation of AMPH or MDMA-induced transmitte r release by reserpine is thought to be counteracted by a reserpine-in duced replenishment of stores. Therefore, all doses of D-amphetamine m ay 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. (C) 1998 Elsevier Science B.V. All r ights reserved.