5-HT2 receptors exert a state-dependent regulation of dopaminergic function: studies with MDL 100,907 and the amphetamine analogue, 3,4-methylenedioxymethamphetamine
Christopher J. Schmidt, Gina M. Fadayel, Christine K. Sullivan, Vicki L. Taylor
European Journal of Pharmacology November 1, 1992 DOI: 10.1016/0014-2999(92)90819-p (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Interventions | MDL 100 907 |
| Topics | MDMA Serotonin |
| Keywords | Dopaminergic Amphetamine Pharmacology Dopamine receptor Nomifensine Microdialysis Endocrinology |
| Citations | 162 |
| Key findings | 5-HT2 receptor blockade with MDL 100,907 attenuated MDMA-induced increases in dopamine synthesis and extracellular striatal dopamine, but did not affect dopamine synthesis or release stimulated by haloperidol or reserpine. |
Abstract
The highly selective 5-HT2 receptor antagonist, MDL 100,907, was used to explore the role of serotonin in the stimulation of dopaminergic function produced by the amphetamine analogue 3,4-methylenedioxymethamphetamine (MDMA). MDL 100,907 blocked MDMA-stimulated dopamine synthesis in vivo without affecting basal synthesis. The long-term deficits in 5-HT concentrations believed to be a consequence of MDMA-induced dopamine release were also blocked by MDL 100,907 over the same dose range. In vivo microdialysis confirmed that 5-HT2 receptor blockade with MDL 100,907 attenuated MDMA-induced increases in extracellular concentrations of striatal dopamine. In contrast to its effect on MDMA-induced synthesis, MDL 100,907 did not alter dopamine synthesis stimulated by haloperidol or reserpine. In vivo dopamine release produced by haloperidol was also unaffected by MDL 100,907. The results suggest a permissive role for 5-HT2 receptors in the activation of the dopamine system which occurs during states of high serotonergic activity or during conditions of elevated dopamine efflux with high D2 receptor occupancy.
Comparable studies
Other experimental studies on MDMA, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin | 2000 | Experimental study | |
| Methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA) cause selective ablation of serotonergic axon terminals in forebrain: immunocytochemical evidence for neurotoxicity Rat brain | 1988 | Experimental study | |
| The molecular mechanism of "ecstasy" [3,4-methylenedioxy-methamphetamine (MDMA)]: serotonin transporters are targets for MDMA-induced serotonin release. Human platelet plasma membrane vesicles and bovine adrenal chromaffin granule membrane... | 1992 | Laboratory study | |
| Oxytocin-dependent reopening of a social reward learning critical period with MDMA | 2019 | Experimental study | |
| Effects of certain hallucinogenic amphetamine analogs on the release of [3H]-serotonin from rat brain synaptosomes Rat whole brain synaptosomes | 1982 | Experimental study |
Citations in the library
Cited by 21
- The pharmacology of the acute hyperthermic response that follows administration of 3,4‐methylenedioxymethamphetamine (MDMA, ‘ecstasy’) to rats British Journal of Pharmacology 2002
- Potentiation of 3,4-methylenedioxymethamphetamine-induced dopamine release and serotonin neurotoxicity by 5-HT2 receptor agonists. European Journal of Pharmacology November 3, 1994
- Blockade of Striatal 5‐Hydroxytryptmine2Receptors Reduces the Increase in Extracellullar Concentrations of Dopamine Produced by the Amphhetamine analogue 3,4‐Methylenedioxymethamphetamine Journal of Neurochemistry April 1, 1994
- Acute Psychological and Neurophysiological Effects of MDMA in Humans Journal of Psychoactive Drugs June 1, 2002
- The abused drug MDMA (Ecstasy) induces programmed death of human serotonergic cells The FASEB Journal February 1, 1997
and 16 more in the library
Cites 9
- Methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA) cause selective ablation of serotonergic axon terminals in forebrain: immunocytochemical evidence for neurotoxicity Journal of Neuroscience August 1, 1988
- Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Journal of Pharmacology and Experimental Therapeutics 1987
- 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Journal of Pharmacology and Experimental Therapeutics September 1, 1987
- Selective 5-hydroxytryptamine2 receptor antagonists protect against the neurotoxicity of methylenedioxymethamphetamine in rats. Journal of Pharmacology and Experimental Therapeutics November 1, 1990
- Effect of 3,4‐Methylenedioxymethamphetamine on 3,4‐Dihydroxyphenylalanine Accumulation in the Striatum and Nucleus Accumbens Journal of Neurochemistry March 1, 1990
and 4 more in the library