Serotonin–GABA interactions modulate MDMA‐induced mesolimbic dopamine release
Journal of Neurochemistry – October 27, 2004
Source: OpenAlex
Summary
MDMA significantly boosts serotonin levels, with a remarkable 1037% increase in the ventral tegmental area (VTA) at a 5 mg/kg dose. This surge in serotonin correlates with a substantial rise in dopamine concentrations in the nucleus accumbens, peaking at 1320%. Additionally, GABA efflux in the VTA increased by up to 229%, influenced by serotonin receptor activity. The selective dopamine releaser d-amphetamine also elevated GABA levels by 180% but did not affect serotonin, highlighting complex interactions among neurotransmitters during MDMA exposure.
Abstract
Abstract 3,4,‐Methylenedioxymethamphetamine (MDMA; ‘ecstasy’) acts at monoamine nerve terminals to alter the release and re‐uptake of dopamine and 5‐HT. The present study used microdialysis in awake rats to measure MDMA‐induced changes in extracellular GABA in the ventral tegmental area (VTA), simultaneous with measures of extracellular dopamine (DA) in the nucleus accumbens (NAC) shell. (+)‐MDMA (0, 2.5, 5 and 10 mg/kg, i.p.) increased GABA efflux in the VTA with a bell‐shaped dose–response. This increase was blocked by application of TTX through the VTA probe. MDMA (5 mg/kg) increased 5‐HT efflux in VTA by 1037% ( p < 0.05). The local perfusion of the 5‐HT 2B/2C antagonist SB 206553 into the VTA reduced VTA GABA efflux after MDMA from a maximum of 229% to a maximum of 126% of basal values ( p < 0.05), while having no effect on basal extracellular GABA concentrations. DA concentrations measured simultaneously in the NAC shell were increased from a maximum of 486% to 1320% ( p < 0.05). The selective DA releaser d‐amphetamine (AMPH) (4 mg/kg) also increased VTA GABA efflux (180%), did not alter 5‐HT and increased NAC DA (875%) ( p < 0.05), but the perfusion of SB 206553 into the VTA failed to alter these effects. These results suggest that MDMA‐mediated increases in DA within the NAC shell are dampened by increases in VTA GABA subsequent to activation of 5‐HT 2B/2C receptors in the VTA.