Serotonin–GABA interactions modulate MDMA‐induced mesolimbic dopamine release
Michael G. Bankson, Bryan K. Yamamoto
Journal of Neurochemistry October 27, 2004 DOI: 10.1111/j.1471-4159.2004.02763.x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Awake rats |
| Interventions | (+)‐MDMA d‐amphetamine SB 206553 TTX |
| Dose | 0, 2.5, 5 and 10 mg/kg MDMA; 5 mg/kg MDMA for 5-HT measurement; 4 mg/kg d-amphetamine |
| Topics | MDMA Serotonin |
| Keywords | Ventral tegmental area Microdialysis Nucleus accumbens Dopamine Pharmacology Monoamine neurotransmitter Extracellular Methamphetamine Endocrinology |
| Citations | 84 |
| Key findings | MDMA increases GABA efflux in the VTA via 5-HT2B/2C receptors, which dampens the concurrent increase in dopamine in the nucleus accumbens shell. |
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.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 23
- Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms Pharmacological Reviews December 16, 2020
- Serotonin 5-HT2BReceptors Are Required for 3,4-Methylenedioxymethamphetamine-Induced Hyperlocomotion and 5-HT ReleaseIn VivoandIn Vitro Journal of Neuroscience March 12, 2008
- The ugly side of amphetamines: short- and long-term toxicity of 3,4-methylenedioxymethamphetamine (MDMA, ‘Ecstasy’), methamphetamine and d-amphetamine Biological Chemistry January 2, 2011
- MDMA-assisted therapy: A new treatment model for social anxiety in autistic adults. Progress in Neuro-Psychopharmacology and Biological Psychiatry January 4, 2016
- Role of Serotonin via 5-HT2B Receptors in the Reinforcing Effects of MDMA in Mice PLoS One November 20, 2009
and 18 more in the library
Cites 9
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- 5-HT2 receptors exert a state-dependent regulation of dopaminergic function: studies with MDL 100,907 and the amphetamine analogue, 3,4-methylenedioxymethamphetamine European Journal of Pharmacology November 1, 1992
- The acute effects of amphetamine derivatives on extracellular serotonin and dopamine levels in rat nucleus accumbens. Pharmacology, Biochemistry, and Behavior April 1998
and 4 more in the library