Methylenedioxymethamphetamine (MDMA): Serotonergic and dopaminergic mechanisms related to its use and misuse

Schenk, Susan; Highgate, Quenten

doi:10.1111/jnc.15348

Cited by 48Neurotransmitter Receptor Influence on BehaviorPsychedelics and Drug StudiesNeuroscience and Neuropharmacology Research

Methylenedioxymethamphetamine (MDMA): Serotonergic and dopaminergic mechanisms related to its use and misuse

Schenk, Susan, Highgate, Quenten·2021·Journal of Neurochemistry

DOI 10.1111/jnc.15348

Open this paper in CoChat — free account

Abstract

Methylenedioxymethamphetamine (MDMA) is an amphetamine analogue that preferentially stimulates the release of serotonin (5HT) and results in relatively small increases in synaptic dopamine (DA). The ratio of drug‐stimulated increases in synaptic DA, relative to 5HT, predicts the abuse liability; drugs with higher DA:5HT ratios are more likely to be abused. Nonetheless, MDMA is a drug that is misused. Clinical and preclinical studies have suggested that repeated MDMA exposure produces neuroadaptive responses in both 5HT and DA neurotransmission that might explain the development and maintenance of MDMA self‐administration in some laboratory animals and the development of a substance use disorder in some humans. In this paper, we describe the research that has demonstrated an inhibitory effect of 5HT on the acquisition of MDMA self‐administration and the critical role of DA in the maintenance of MDMA self‐administration in laboratory animals. We then describe the circuitry and 5HT receptors that are positioned to modulate DA activity and review the limited research on the effects of MDMA exposure on these receptor mechanisms. image

Integrity signals

Registry

Crossref · 10.1111/jnc.15348

Cites

132 of 132 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Different classes of drugs increase dopamine via distinct molecular targets and mechanisms, with resultant differences in the magnitude and the speed of dopamine increase, which in turn are factors that contribute to a drug's addictive liability.
“Different classes of drugs increase dopamine via distinct molec ular targets and mechanisms (see Table3), with resultant differenc es in the magnitude and the speed of dopamine increase, which in turn are factors that contribute to a drug's addictive liability 36 .”
From Substance use disorders: a comprehensive update of classification, epidemiology, neurobiology, clinical aspects, treatment and prevention (2023) · cites this paper as [36]

Neurocircuitry of Addiction
Koob, G. F., & Volkow, N. D. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2009.110 · Cited by 5,340 · see citing works
Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats.
Di Chiara, G., & Imperato, A. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.14.5274 · Cited by 4,733 · see citing works
Neurobiology of addiction: a neurocircuitry analysis
Koob, G. F., & Volkow, N. D. (2016) · The Lancet Psychiatry · doi:10.1016/s2215-0366(16)00104-8 · Cited by 3,698 · see citing works
A review of central 5-HT receptors and their function
Barnes, N. M., & Sharp, T. (1999) · Neuropharmacology · doi:10.1016/s0028-3908(99)00010-6 · Cited by 3,150 · see citing works
Structure and function of the brain serotonin system
Jacobs, B. L., & Azmitia, E. C. (1992) · Physiological Reviews · doi:10.1152/physrev.1992.72.1.165 · Cited by 2,574 · see citing works
Quantitative autoradiographic mapping of serotonin receptors in the rat brain. I. Serotonin-1 receptors
Pazos, Á., & Palacios, J. M. (1985) · Brain Research · doi:10.1016/0006-8993(85)90856-x · Cited by 1,855 · see citing works
The Pharmacology and Clinical Pharmacology of 3,4-Methylenedioxymethamphetamine (MDMA, “Ecstasy”)
Green, A. R., Mechan, A. O., Elliott, J. M., O’Shea, E., & Colado, M. I. (2003) · Pharmacological Reviews · doi:10.1124/pr.55.3.3 · Cited by 1,272 · see citing works
Transition from Moderate to Excessive Drug Intake: Change in Hedonic Set Point
Ahmed, S. H., & Koob, G. F. (1998) · Science · doi:10.1126/science.282.5387.298 · Cited by 1,159 · see citing works
Addiction: Beyond dopamine reward circuitry
Volkow, N. D., Wang, G.-J., Fowler, J. S., Tomasi, D., & Telang, F. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1010654108 · Cited by 959 · see citing works
The Neuroscience of Drug Reward and Addiction
Volkow, N. D., Michaelides, M., & Baler, R. (2019) · Physiological Reviews · doi:10.1152/physrev.00014.2018 · Cited by 863 · cited 1× · see citing works
“Many of these neuroadaptations have been previously described (Koob & Volkow, 2010, 2016; Volkow et al., 2011, 2019) and occur following repeated exposure to drugs that are misused.”
Background
Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission
Alex, K. D., & Pehek, E. A. (2006) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2006.08.004 · Cited by 658 · see citing works
Autoregulation of Serotonin Neurons: Role in Antidepressant Drug Action
Piñeyro, G., & Blier, P. (1999) · Pharmacological Reviews · doi:10.1016/s0031-6997(24)01417-0 · Cited by 537 · see citing works
Anatomically defined and functionally distinct dorsal raphe serotonin sub-systems
Ren, J., Friedmann, D., Xiong, J., Liu, C. D., Ferguson, B. R., Weerakkody, T., DeLoach, K. E., Ran, C., Pun, A., Sun, Y., et al. (2018) · Cell · doi:10.1016/j.cell.2018.07.043 · Cited by 498 · see citing works
Serotonin modulation of cortical neurons and networks
Celada, P., Puig, M. V., & Artigas, F. (2013) · Frontiers in Integrative Neuroscience · doi:10.3389/fnint.2013.00025 · Cited by 462 · see citing works
Dopamine neurons create Pavlovian conditioned stimuli with circuit-defined motivational properties
Saunders, B. T., Richard, J. M., Margolis, E. B., & Janak, P. H. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0191-4 · Cited by 365 · see citing works
Control of Serotonergic Function in Medial Prefrontal Cortex by Serotonin-2A Receptors through a Glutamate-Dependent Mechanism
Martín‐Ruiz, R., Puig, M. V., Celada, P., Shapiro, D. A., Roth, B. L., Mengod, G., & Artigas, F. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-24-09856.2001 · Cited by 338 · see citing works
Animal models of drug relapse and craving
Vènniro, M., Caprioli, D., & Shaham, Y. (2015) · Progress in brain research · doi:10.1016/bs.pbr.2015.08.004 · Cited by 322 · see citing works
Untitled work
(1988) · PubMed · Cited by 313 · see citing works
Molecular and Cellular Mechanisms of Ecstasy-Induced Neurotoxicity: An Overview
Capela, J. P., Carmo, H., Remião, F., Bastos, M. D. L., Meisel, A., & Carvalho, F. D. (2009) · Molecular Neurobiology · doi:10.1007/s12035-009-8064-1 · Cited by 285 · see citing works
Mood and cognitive effects of 6 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy'): week-end 'high' followed by mid-week low
Curran, H. V., & Travill, R. A. (1997) · Addiction · doi:10.1111/j.1360-0443.1997.tb02951.x · Cited by 284 · see citing works
The efferent connection of the nucleus raphe dorsalis
Pierce, E. T., Foote, W. E., & Hobson, J. A. (1976) · Brain Research · doi:10.1016/0006-8993(76)90102-5 · Cited by 269 · see citing works
Carrier‐Mediated Release of Serotonin by 3,4‐Methylenedioxymethamphetamine: Implications for Serotonin‐Dopamine Interactions
Gudelsky, G. A., & Nash, J. F. (1996) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1996.66010243.x · Cited by 252 · see citing works
Acute psychological effects of 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”) are attenuated by the serotonin uptake inhibitor citalopram
Liechti, M. (2000) · Neuropsychopharmacology · doi:10.1016/s0893-133x(99)00148-7 · Cited by 248 · see citing works
Psychological and Physiological Effects of MDMA (“Ecstasy”) after Pretreatment with the 5-HT2 Antagonist Ketanserin in Healthy Humans
Liechti, M. (2000) · Neuropsychopharmacology · doi:10.1016/s0893-133x(00)00126-3 · Cited by 245 · see citing works
High versus low reactivity to a novel environment: behavioural, pharmacological and neurochemical assessments
Thiel, C. M., Müller, C. P., Huston, J. P., & Schwarting, R. K. W. (1999) · Neuroscience · doi:10.1016/s0306-4522(99)00158-x · Cited by 241 · see citing works
Localization of the mRNA for the 5-HT2 receptor by in situ hybridization histochemistry. Correlation with the distribution of receptor sites
Mengod, G., Pompeiano, M., ́nez-Mir, M. I. M., & Palacios, J. M. (1990) · Brain Research · doi:10.1016/0006-8993(90)90502-3 · Cited by 240 · see citing works
Chronic tolerance to recreational MDMA (3,4-methylenedioxymethamphetamine) or Ecstasy
Parrott, A. C. (2005) · Journal of Psychopharmacology · doi:10.1177/0269881105048900 · Cited by 238 · see citing works
Central 5-HT receptors and their function; present and future
Sharp, T., & Barnes, N. M. (2020) · Neuropharmacology · doi:10.1016/j.neuropharm.2020.108155 · Cited by 227 · see citing works
Vesicular glutamate transporter 3‐expressing nonserotonergic projection neurons constitute a subregion in the rat midbrain raphe nuclei
Hioki, H., Nakamura, H., Ma, Y., Konno, M., Hayakawa, T., Nakamura, K., Fujiyama, F., & Kaneko, T. (2009) · The Journal of Comparative Neurology · doi:10.1002/cne.22237 · Cited by 218 · see citing works
Effects of extended access to high versus low cocaine doses on self-administration, cocaine-induced reinstatement and brain mRNA levels in rats
Mantsch, J. R., Yuferov, V. P., Mathieu-Kia, A.-M., Ho, A., & Kreek, M. J. (2004) · Psychopharmacology · doi:10.1007/s00213-004-1778-x · Cited by 214 · see citing works
Relationship between the Serotonergic Activity and Reinforcing Effects of a Series of Amphetamine Analogs
Wee, S., Anderson, K. G., Baumann, M. H., Rothman, R. B., Blough, B. E., & Woolverton, W. L. (2005) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.104.080101 · Cited by 211 · see citing works
Cocaine-induced alterations in dopamine receptor signaling: Implications for reinforcement and reinstatement
Anderson, S. M., & Pierce, R. C. (2005) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2004.12.004 · Cited by 200 · see citing works
A glutamatergic reward input from the dorsal raphe to ventral tegmental area dopamine neurons
Qi, J., Zhang, S. S., Wang, H., Wang, H., Buendia, J. D. J. A., Hoffman, A. F., Lupica, C. R., Seal, R. P., & Morales, M. (2014) · Nature Communications · doi:10.1038/ncomms6390 · Cited by 195 · see citing works
Human psychobiology of MDMA or ‘Ecstasy’: an overview of 25 years of empirical research
Parrott, A. C. (2013) · Human Psychopharmacology Clinical and Experimental · doi:10.1002/hup.2318 · Cited by 185 · see citing works
The subjective effects of MDMA and mCPP in moderate MDMA users
Tancer, M. E., & Johanson, C. (2001) · Drug and Alcohol Dependence · doi:10.1016/s0376-8716(01)00146-6 · Cited by 179 · see citing works
Ultrastructural localization of the serotonin 2A receptor in dopaminergic neurons in the ventral tegmental area
Doherty, M. D., & Pickel, V. M. (2000) · Brain Research · doi:10.1016/s0006-8993(00)02062-x · Cited by 178 · see citing works
Relationship between self-administration of amphetamine and monoamine receptors in brain: comparison with cocaine.
Ritz, M. C., & Kuhar, M. J. (1989) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)24116-7 · Cited by 176 · see citing works
Dorsal raphe dual serotonin-glutamate neurons drive reward by establishing excitatory synapses on VTA mesoaccumbens dopamine neurons
Wang, H.-L., Zhang, S., Qi, J., Wang, H., Cachope, R., Mejias-Aponte, C. A., Gomez, J. A., Mateo-Semidey, G. E., Beaudoin, G. M. J., Paladini, C. A., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.01.014 · Cited by 176 · see citing works
Ecstasy abuse and dependence among adolescents and young adults: applicability and reliability of DSM‐IV criteria
Cottler, L. B., Womack, S. B., Compton, W. M., & Abdallah, A. B. (2001) · Human Psychopharmacology Clinical and Experimental · doi:10.1002/hup.343 · Cited by 172 · see citing works
Understanding Addiction Using Animal Models
Kuhn, B. N., Kalivas, P. W., & Bobadilla, A. (2019) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2019.00262 · Cited by 171 · see citing works
Acquisition of IV amphetamine and cocaine self-administration in rats as a function of dose
Carroll, M. E., & Lac, S. T. (1997) · Psychopharmacology · doi:10.1007/s002130050182 · Cited by 162 · see citing works
Distribution of serotonin 5-HT2C receptors in the ventral tegmental area
Bubar, M. J., & Cunningham, K. A. (2007) · Neuroscience · doi:10.1016/j.neuroscience.2006.12.071 · Cited by 162 · see citing works
MDMA Elicits Behavioral and Neurochemical Sensitization in Rats
Kalivas, P. W. (1998) · Neuropsychopharmacology · doi:10.1016/s0893-133x(97)00195-4 · Cited by 158 · see citing works
Acute and long-term effects of MDMA on cerebral dopamine biochemistry and function
Colado, M. I., O’Shea, E., & Green, A. R. (2004) · Psychopharmacology · doi:10.1007/s00213-004-1788-8 · Cited by 153 · see citing works
Reinforcing, subjective, and physiological effects of MDMA in humans: A comparison with d-amphetamine and mCPP
Tancer, M., & Johanson, C.-E. (2003) · Drug and Alcohol Dependence · doi:10.1016/s0376-8716(03)00172-8 · Cited by 153 · see citing works
Development, maintenance and temporal pattern of self-administration maintained by ecstasy (MDMA) in rats
Schenk, S., Gittings, D., Johnstone, M., & Daniela, E. (2003) · Psychopharmacology · doi:10.1007/s00213-003-1407-0 · Cited by 146 · see citing works
Self-citation
Acute psychological and physiological effects of MDMA (“Ecstasy”) after haloperidol pretreatment in healthy humans
Liechti, M. E., & Vollenweider, F. X. (2000) · European Neuropsychopharmacology · doi:10.1016/s0924-977x(00)00086-9 · Cited by 145 · see citing works
Self-administration of methylenedioxymethamphetamine (MDMA) by rhesus monkeys
Beardsley, P. M., Balster, R. L., & Harris, L. S. (1986) · Drug and Alcohol Dependence · doi:10.1016/0376-8716(86)90047-5 · Cited by 141 · see citing works
Role of Serotonin in Central Dopamine Dysfunction
Giovanni, G. D., Esposito, E., & Matteo, V. D. (2010) · CNS Neuroscience & Therapeutics · doi:10.1111/j.1755-5949.2010.00135.x · Cited by 139 · see citing works
3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") and its stereoisomers as reinforcers in rhesus monkeys: serotonergic involvement
Fantegrossi, W. E., Ullrich, T., Rice, K. C., Woods, J. H., & Winger, G. D. (2002) · Psychopharmacology · doi:10.1007/s00213-002-1021-6 · Cited by 139 · see citing works
Is ecstasy a drug of dependence?
Degenhardt, L. J., Bruno, R., & Topp, L. (2009) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2009.09.009 · Cited by 137 · see citing works
Locomotor stimulation produced by 3,4-methylenedioxymethamphetamine (MDMA) is correlated with dialysate levels of serotonin and dopamine in rat brain
Baumann, M. H., Clark, R. D., & Rothman, R. B. (2008) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2008.02.018 · Cited by 135 · see citing works
Development and expression of sensitization to cocaine's reinforcing properties: role of NMDA receptors
Schenk, S., Valadez, A. A., McNamara, C., et al. (1993) · Psychopharmacology · doi:10.1007/bf02244949 · Cited by 134 · see citing works
Self-citation
Self-injection of d,1-3,4-methylenedioxymethamphetamine (MDMA) in the baboon
Lamb, R. J., & Griffiths, R. R. (1987) · Psychopharmacology · doi:10.1007/bf00518175 · Cited by 127 · see citing works
Synaptic structure and connectivity of serotonin terminals in the ventral tegmental area: potential sites for modulation of mesolimbic dopamine neurons
Bockstaele, E. J. V., Cestari, D. M., & Pickel, V. M. (1994) · Brain Research · doi:10.1016/0006-8993(94)91330-7 · Cited by 126 · see citing works
Ecstasy: Are animal data consistent between species and can they translate to humans?
Easton, N., & Marsden, C. A. (2006) · Journal of Psychopharmacology · doi:10.1177/0269881106061153 · Cited by 126 · see citing works
Ecstasy (MDMA) dependence
Jansen, K. (1999) · Drug and Alcohol Dependence · doi:10.1016/s0376-8716(98)00111-2 · Cited by 125 · see citing works
Increased Anxiety 3 Months after Brief Exposure to MDMA (‘Ecstasy’) in Rats: Association with Altered 5-HT Transporter and Receptor Density
McGregor, I. S., Clemens, K. J., Plasse, G., Li, K. M., Hunt, G. E., Chen, F., & Lawrence, A. J. (2003) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300185 · Cited by 122 · see citing works
A neurotoxic regimen of MDMA suppresses behavioral, thermal and neurochemical responses to subsequent MDMA administration
Shankaran, M., & Gudelsky, G. A. (1999) · Psychopharmacology · doi:10.1007/s002130051143 · Cited by 122 · see citing works
A direct comparison of the behavioral and physiological effects of methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) in humans
Kirkpatrick, M. G., Gunderson, E. W., Perez, A. Y., Haney, M., Foltin, R. W., & Hart, C. L. (2011) · Psychopharmacology · doi:10.1007/s00213-011-2383-4 · Cited by 120 · see citing works
Behavioral and Neurochemical Consequences of Long-Term Intravenous Self-Administration of MDMA and Its Enantiomers by Rhesus Monkeys
Fantegrossi, W. E., Woolverton, W. L., Kilbourn, M. R., Sherman, P. S., Yuan, J., Hatzidimitriou, G., Ricaurte, G. A., Woods, J. H., & Winger, G. D. (2004) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300442 · Cited by 117 · see citing works
Effect of SCH 23390 on (±)-3,4-methylenedioxymethamphetamine hyperactivity and self-administration in rats
Daniela, E. J. K., Brennan, K., Gittings, D., Hely, L. S., & Schenk, S. (2004) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2004.01.008 · Cited by 113 · see citing works
Self-citation
MDMA self‐administration in rats: acquisition, progressive ratio responding and serotonin transporter binding
Schenk, S., Hely, L. S., Lake, B., Daniela, E. J. K., Gittings, D., & Mash, D. C. (2007) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2007.05932.x · Cited by 107 · see citing works
Self-citation
Incidence and patterns of polydrug use and craving for ecstasy in regular ecstasy users: An ecological momentary assessment study
Hopper, J. W., Su, Z., Looby, A. R., Ryan, E. T., Penetar, D. M., Palmer, C. M., & Lukas, S. E. (2006) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2006.04.012 · Cited by 105 · see citing works
Modeling Relapse in Animals
Martin‐Fardon, R., & Weiss, F. (2012) · Current topics in behavioral neurosciences · doi:10.1007/7854_2012_202 · Cited by 101 · see citing works
Reinforcing Effects of MDMA (‘Ecstasy’) in Drug-Naive and Cocaine-Trained Rats
Ratzenboeck, E., Saria, A., Kriechbaum, N., et al. (2001) · Pharmacology · doi:10.1159/000056086 · Cited by 95 · see citing works
Intravenous self-administration of mephedrone, methylone and MDMA in female rats
Creehan, K. M., Vandewater, S. A., & Taffe, M. A. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2015.01.003 · Cited by 92 · see citing works
3,4-Methylenedioxymethamphetamine Self-Administration is Abolished in Serotonin Transporter Knockout Mice
Trigo, J. M., Renoir, T., Lanfumey, L., Hamon, M., Lesch, K., Robledo, P., & Maldonado, R. J. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.11.005 · Cited by 91 · see citing works
Serotonin–dopamine interaction: an overview
ESPOSITO, E., DIMATTEO, V, & DIGIOVANNI, G. (2008) · Progress in Brain Research · doi:10.1016/s0079-6123(08)00901-1 · Cited by 88 · see citing works
Effect of D1-like and D2-like receptor antagonists on methamphetamine and 3,4-methylenedioxymethamphetamine self-administration in rats
Brennan, K. A., Carati, C., Lea, R. A., Fitzmaurice, P. S., & Schenk, S. (2009) · Behavioural Pharmacology · doi:10.1097/fbp.0b013e328333a28d · Cited by 88 · see citing works
Self-citation
Relevance of rodent models of intravenous MDMA self-administration to human MDMA consumption patterns
Garza, R. D. L., Fabrizio, K., & Gupta, A. (2006) · Psychopharmacology · doi:10.1007/s00213-005-0255-5 · Cited by 74 · see citing works
Modeling Relapse in Animals
Martin‐Fardon, R., & Weiss, F. (2012) · Current topics in behavioral neurosciences · doi:10.1007/978-3-642-28720-6_202 · Cited by 70 · see citing works
Evidence for Chronically Altered Serotonin Function in the Cerebral Cortex of Female 3,4-Methylenedioxymethamphetamine Polydrug Users
Watkins, T. J. (2011) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2011.156 · Cited by 68 · see citing works
Estimating the relative reinforcing strength of (±)-3,4-methylenedioxymethamphetamine (MDMA) and its isomers in rhesus monkeys: comparison to (+)-methamphetamine
Wang, Z., & Woolverton, W. L. (2006) · Psychopharmacology · doi:10.1007/s00213-006-0599-5 · Cited by 66 · see citing works
A reliable model of intravenous MDMA self-administration in naïve mice
Trigo, J. M., Panayi, F., Sòria, G., Maldonado, R. J., & Robledo, P. (2005) · Psychopharmacology · doi:10.1007/s00213-005-0229-7 · Cited by 66 · see citing works
Problematic versus non-problematic ecstasy/MDMA use: the influence of drug usage patterns and pre-existing psychiatric factors
Soar, K., Turner, J. J., & Parrott, A. C. (2006) · Journal of Psychopharmacology · doi:10.1177/0269881106063274 · Cited by 65 · see citing works
Expression of 5-HT2A receptors in prefrontal cortex pyramidal neurons projecting to nucleus accumbens. Potential relevance for atypical antipsychotic action.
Mocci, G., Jiménez-Sánchez, L., Adell, A., Cortés, R., & Artigas, F. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.10.021 · Cited by 64 · see citing works
A comparison of the reinforcing efficacy of 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”) with cocaine in rhesus monkeys
Lile, J. A., Ross, J. T., & Nader, M. A. (2004) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2004.10.006 · Cited by 63 · see citing works
Brain Serotonin Function in MDMA (Ecstasy) Users: Evidence for Persisting Neurotoxicity
Benningfield, M. M., & Cowan, R. L. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2012.178 · Cited by 61 · see citing works
Effects of MDMA on Extracellular Dopamine and Serotonin Levels in Mice Lacking Dopamine and/or Serotonin Transporters
Hagino, Y., Takamatsu, Y., Yamamoto, H., Iwamura, T., Murphy, D. L., Uhl, G. R., Sora, I., & Ikeda, K. (2011) · Current Neuropharmacology · doi:10.2174/157015911795017254 · Cited by 60 · see citing works
Dopaminergic mechanisms of reinstatement of MDMA‐seeking behaviour in rats
Schenk, S., Gittings, D., & Colussi‐Mas, J. (2010) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2010.01193.x · Cited by 59 · see citing works
Self-citation
Acquisition of MDMA self‐administration: pharmacokinetic factors and MDMA ‐induced serotonin release
Bradbury, S., Bird, J., Colussi‐Mas, J., Mueller, M., Ricaurte, G. A., & Schenk, S. (2013) · Addiction Biology · doi:10.1111/adb.12069 · Cited by 59 · see citing works
Self-citation
Sustained Recreational Use of Ecstasy Is Associated with Altered Pre and Postsynaptic Markers of Serotonin Transmission in Neocortical Areas: A PET Study with [11C]DASB and [11C]MDL 100907
Urban, N., Girgis, R. R., Talbot, P. S., Kegeles, L. S., Xu, X., Frankle, W. G., Hart, C. L., Slifstein, M., Abi‐Dargham, A., & Laruelle, M. A. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2011.332 · Cited by 59 · see citing works
Discriminative stimulus effects of 3,4-methylenedioxymethamphetamine (MDMA) in humans trained to discriminate among d-amphetamine, meta-chlorophenylpiperazine and placebo
Johanson, C.-E., Kilbey, M., Gatchalian, K., & Tancer, M. (2006) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2005.05.003 · Cited by 58 · see citing works
Test–re‐test reliability of DSM‐IV adopted criteria for 3,4‐methylenedioxymethamphetamine (MDMA) abuse and dependence: a cross‐national study
Cottler, L. B., Leung, K. S., & Abdallah, A. B. (2009) · Addiction · doi:10.1111/j.1360-0443.2009.02649.x · Cited by 56 · see citing works
A genetic deletion of the serotonin transporter greatly enhances the reinforcing properties of MDMA in rats
Oakly, A., Brox, B. W., Schenk, S., & Ellenbroek, B. A. (2013) · Molecular Psychiatry · doi:10.1038/mp.2013.75 · Cited by 53 · see citing works
Self-citation
Repeated administration of MDMA causes transient down-regulation of serotonin 5-HT2 receptors
Scheffel, U., Lever, J. R., Stathis, M., & Ricaurte, G. A. (1992) · Neuropharmacology · doi:10.1016/0028-3908(92)90126-a · Cited by 52 · see citing works
Methylenedioxymethamphetamine induces opposite changes in central pre- and postsynaptic 5-HT1A receptors in rats
Aguirre, N., Galbete, J., Lasheras, B., & Rı́o, J. D. (1995) · European Journal of Pharmacology · doi:10.1016/0014-2999(95)00303-3 · Cited by 51 · see citing works
Effects of priming injections of MDMA and cocaine on reinstatement of MDMA- and cocaine-seeking in rats
Schenk, S., Hely, L. S., Gittings, D., Lake, B., & Daniela, E. (2008) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2008.03.014 · Cited by 49 · see citing works
Self-citation
Quantitative mapping shows that serotonin rather than dopamine receptor mRNA expressions are affected after repeated intermittent administration of MDMA in rat brain
Kindlundh-Högberg, A. M. S., Svenningsson, P., & Schiöth, H. B. (2006) · Neuropharmacology · doi:10.1016/j.neuropharm.2006.05.026 · Cited by 47 · see citing works
Behavioral, thermal and neurochemical effects of acute and chronic 3,4-methylenedioxymethamphetamine (“Ecstasy”) self-administration
Reveron, M. E., Maier, E. Y., & Duvauchelle, C. L. (2009) · Behavioural Brain Research · doi:10.1016/j.bbr.2009.10.038 · Cited by 46 · see citing works
Effects of 3,4‐methylenedioxymethamphetamine (MDMA) on serotonin transporter and vesicular monoamine transporter 2 protein and gene expression in rats: implications for MDMA neurotoxicity
Biezonski, D. K., & Meyer, J. S. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06515.x · Cited by 46 · see citing works
Differential involvement of prelimbic and infralimbic medial prefrontal cortex in discrete cue-induced reinstatement of 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) seeking in rats
Ball, K. T., & Slane, M. M. (2012) · Psychopharmacology · doi:10.1007/s00213-012-2762-5 · Cited by 45 · see citing works
Nonhuman animal models of substance use disorders: Translational value and utility to basic science
Smith, M. A. (2019) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2019.107733 · Cited by 45 · see citing works
MDMA (“ecstasy”) abuse as an example of dopamine neuroplasticity
Schenk, S. (2010) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2010.12.010 · Cited by 43 · see citing works
Self-citation
The sub-acute effects of recreational ecstasy (MDMA) use: a controlled study in humans
Huxster, J. K., Pirona, A., & Morgan, M. J. (2006) · Journal of Psychopharmacology · doi:10.1177/0269881106060513 · Cited by 43 · see citing works
The effects of ecstasy on neurotransmitter systems: a review on the findings of molecular imaging studies
Vegting, Y., Reneman, L., & Booij, J. (2016) · Psychopharmacology · doi:10.1007/s00213-016-4396-5 · Cited by 42 · see citing works
Reinstatement of MDMA (ecstasy) seeking by exposure to discrete drug-conditioned cues
Ball, K. T., Walsh, K. M., & Rebec, G. V. (2007) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2007.05.018 · Cited by 41 · see citing works
Drug seeking in response to a priming injection of MDMA in rats: relationship to initial sensitivity to self-administered MDMA and dorsal striatal dopamine
Colussi‐Mas, J., Wise, R. J., Howard, A., & Schenk, S. (2010) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145710000283 · Cited by 41 · see citing works
Self-citation
Chronic eticlopride and dopamine denervation induce equal nonadditive increases in striatal D2 receptor density: Autoradiographic evidence against the dual mechanism hypothesis
LaHoste, G. J., & Marshall, J. F. (1991) · Neuroscience · doi:10.1016/0306-4522(91)90342-l · Cited by 40 · see citing works
Repeated Adolescent 3,4-Methylenedioxymethamphetamine (MDMA) Exposure in Rats Attenuates the Effects of a Subsequent Challenge with MDMA or a 5-Hydroxytryptamine1A Receptor Agonist
Piper, B. J., Vu, H. L., Safain, M. G., Oliver, A. J., & Meyer, J. S. (2006) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.105.095760 · Cited by 40 · see citing works
Involvement of 5-HT2A receptors in MDMA reinforcement and cue-induced reinstatement of MDMA-seeking behaviour
Orejarena, M. J., Lanfumey, L., Maldonado, R. J., & Robledo, P. (2010) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145710001215 · Cited by 38 · see citing works
Self‐administered MDMA produces dose‐ and time‐dependent serotonin deficits in the rat brain
Do, J., & Schenk, S. (2011) · Addiction Biology · doi:10.1111/j.1369-1600.2011.00370.x · Cited by 37 · see citing works
Self-citation
One day access to a running wheel reduces self-administration of d-methamphetamine, MDMA and methylone
Aarde, S. M., Miller, M. L., Creehan, K. M., et al. (2015) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2015.03.016 · Cited by 37 · see citing works
Discriminative-Stimulus, Subject-Rated, and Physiological Effects of Methamphetamine in Humans Pretreated With Aripiprazole
Sevak, R. J., Vansickel, A. R., Stoops, W. W., Glaser, P. E. A., Hays, L. R., & Rush, C. R. (2011) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0b013e318221b2db · Cited by 35 · see citing works
Conditioning following repeated exposure to MDMA in rats: Role in the maintenance of MDMA self-administration.
Daniela, E., Gittings, D., & Schenk, S. (2006) · Behavioral Neuroscience · doi:10.1037/0735-7044.120.5.1144 · Cited by 35 · see citing works
Self-citation
Contribution of impulsivity and novelty-seeking to the acquisition and maintenance of MDMA self-administration
Bird, J., & Schenk, S. (2012) · Addiction Biology · doi:10.1111/j.1369-1600.2012.00477.x · Cited by 32 · see citing works
Self-citation
Symptoms of Ecstasy Dependence and Correlation With Psychopathology in Taiwanese Adolescents
Yen, C., & Hsu, S.-Y. (2007) · The Journal of Nervous and Mental Disease · doi:10.1097/nmd.0b013e3181568625 · Cited by 31 · see citing works
Reinforcing effects of methylenedioxy amphetamine congeners in rhesus monkeys: are intravenous self-administration experiments relevant to MDMA neurotoxicity?
Fantegrossi, W. E. (2006) · Psychopharmacology · doi:10.1007/s00213-006-0320-8 · Cited by 29 · see citing works
The effect of the ecstasy ‘come-down’ on the diagnosis of ecstasy dependence
McKetin, R., Copeland, J., Norberg, M. M., Bruno, R., Hides, L. M., & Khawar, L. (2014) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2014.02.697 · Cited by 27 · see citing works
Effect of the Repeated Administration of (±)-3,4-Methylenedioxymethamphetamine on the Behavioral Response of Rats to the 5-HT1A Receptor Agonist (±)-8-Hydroxy-(di-n-Propylamino)Tetralin
Granoff, M. I., & Ashby, C. R. (2001) · Neuropsychobiology · doi:10.1159/000054864 · Cited by 25 · see citing works
Repeated MDMA administration increases MDMA-produced locomotor activity and facilitates the acquisition of MDMA self-administration: role of dopamine D2 receptor mechanisms.
van de Wetering, R., & Schenk, S. (2017) · Psychopharmacology · doi:10.1007/s00213-017-4554-4 · Cited by 25 · see citing works
Self-citation
Chronic MDMA induces neurochemical changes in the hippocampus of adolescent and young adult rats: Down-regulation of apoptotic markers
García‐Cabrerizo, R., & García-Fuster, M. J. (2015) · NeuroToxicology · doi:10.1016/j.neuro.2015.06.001 · Cited by 24 · see citing works
Tri-city study of Ecstasy use problems: A latent class analysis
Scheier, L. M., Abdallah, A. B., Inciardi, J. A., Copeland, J., & Cottler, L. B. (2008) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2008.06.008 · Cited by 23 · see citing works
PRECLINICAL STUDY: FULL ARTICLE: Tolerance to 3,4‐methylenedioxymethamphetamine is associated with impaired serotonin release
Jones, K. L., Brennan, K. A., Colussi‐Mas, J., & Schenk, S. (2010) · Addiction Biology · doi:10.1111/j.1369-1600.2010.00217.x · Cited by 20 · see citing works
Self-citation
Tolerance to the locomotor-activating effects of 3,4-methylenedioxymethamphetamine (MDMA) predicts escalation of MDMA self-administration and cue-induced reinstatement of MDMA seeking in rats
Ball, K. T., & Slane, M. M. (2014) · Behavioural Brain Research · doi:10.1016/j.bbr.2014.08.010 · Cited by 20 · see citing works
The Prevalence, Intensity, and Assessment of Craving for MDMA/Ecstasy in Recreational Users
Davis, A. K., & Rosenberg, H. (2014) · Journal of Psychoactive Drugs · doi:10.1080/02791072.2014.901586 · Cited by 17 · see citing works
Persistent sensitisation to the locomotor activating effects of MDMA following MDMA self-administration in rats
Schenk, S., & Bradbury, S. (2015) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2015.03.001 · Cited by 16 · see citing works
Self-citation
Escalation of cocaine consumption in short and long access self-administration procedures
Mandt, B. H., Copenhagen, L. I., Zahniser, N. R., & Allen, R. M. (2015) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2015.01.039 · Cited by 16 · see citing works
Serotonin antagonists fail to alter MDMA self-administration in rats
Schenk, S., Foote, J., Aronsen, D., Bukholt, N., Highgate, Q., van de Wetering, R., & Webster, J. (2016) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2016.06.002 · Cited by 16 · see citing works
Self-citation
3,4-Methylenedioxymethamphetamine Induces Gene Expression Changes in Rats Related to Serotonergic and Dopaminergic Systems, But Not to Neurotoxicity
Cuyàs, E., Robledo, P., Pizarro, N., Farré, M., Puerta, E., Aguirre, N., & de la Torre, R. (2013) · Neurotoxicity Research · doi:10.1007/s12640-013-9416-1 · Cited by 15 · see citing works
Repeated administration of the 5-HT1B/1A agonist, RU 24969, facilitates the acquisition of MDMA self-administration: role of 5-HT1A and 5-HT1B receptor mechanisms
Aronsen, D., Bukholt, N., & Schenk, S. (2016) · Psychopharmacology · doi:10.1007/s00213-016-4225-x · Cited by 14 · see citing works
Self-citation
High ambient temperature facilitates the acquisition of 3,4-methylenedioxymethamphetamine (MDMA) self-administration
Aarde, S. M., Huang, P.-K., & Taffe, M. A. (2017) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2017.10.008 · Cited by 14 · see citing works
Antidepressants are not drugs of abuse or dependence
LICHTIGFELD, F. J., & Gillman, M. A. (1998) · Postgraduate Medical Journal · doi:10.1136/pgmj.74.875.529 · Cited by 13 · see citing works
Prevention of drug priming- and cue-induced reinstatement of MDMA-seeking behaviors by the CB1 cannabinoid receptor antagonist AM251
Nawata, Y., Kitaichi, K., & Yamamoto, T. (2015) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2015.12.016 · Cited by 12 · see citing works
Effects of repeated exposure to MDMA on 5HT1a autoreceptor function: behavioral and neurochemical responses to 8-OHDPAT
Schenk, S., Abraham, B., Aronsen, D., Colussi‐Mas, J., & Do, J. (2013) · Psychopharmacology · doi:10.1007/s00213-013-2980-5 · Cited by 11 · see citing works
Self-citation
Comparison of the effects of abstinence on MDMA and cocaine self-administration in rats
Highgate, Q., & Schenk, S. (2018) · Psychopharmacology · doi:10.1007/s00213-018-5026-1 · Cited by 11 · see citing works
Self-citation
Extinction training following cocaine or MDMA self-administration produces discrete changes in D2-like and mGlu5 receptor density in the rat brain
Frankowska, M., Miszkiel, J., Pomierny-Chamioło, L., Pomierny, B., Borelli, A. C., Suder, A., & Filip, M. (2019) · Pharmacological Reports · doi:10.1016/j.pharep.2019.05.001 · Cited by 9 · see citing works
Regional changes in ∆FosB expression in rat brain following MDMA self‐administration predict increased sensitivity to effects of locally infused MDMA
van de Wetering, R., & Schenk, S. (2019) · Addiction Biology · doi:10.1111/adb.12814 · Cited by 9 · see citing works
Self-citation
Contribution of Impulsivity and Serotonin Receptor Neuroadaptations to the Development of an MDMA (‘Ecstasy’) Substance Use Disorder
Schenk, S., & Aronsen, D. (2015) · Current topics in behavioral neurosciences · doi:10.1007/7854_2015_421 · Cited by 4 · see citing works
Self-citation
MDMA self-administration fails to alter the behavioral response to 5-HT1A and 5-HT1B agonists
Aronsen, D., & Schenk, S. (2016) · Psychopharmacology · doi:10.1007/s00213-016-4226-9 · Cited by 1 · see citing works
Self-citation
MDMA (Ecstasy) and Gene Expression in the Brain
Fernàndez‐Castillo, N., Ribasés, M., & Cormand, B. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-800212-4.00039-x · Cited by 1 · see citing works

Flagged first, then by citations

Sorted by citations

Substance use disorders: a comprehensive update of classification, epidemiology, neurobiology, clinical aspects, treatment and prevention
Volkow, N. D., & Blanco, C. (2023) · World psychiatry · doi:10.1002/wps.21073 · Cited by 503 · see citing works

Toxic effects of MDMA on central serotonergic neurons in the primate: importance of route and frequency of drug administration
Ricaurte, G. A., DeLanney, L. E., Irwin, I., & Langston, J. W. (1988) · Brain Research · doi:10.1016/0006-8993(88)91309-1 · Cited by 245 · see citing works
Ecstasy: Are animal data consistent between species and can they translate to humans?
Easton, N., & Marsden, C. A. (2006) · Journal of Psychopharmacology · doi:10.1177/0269881106061153 · Cited by 126 · see citing works
Simultaneous polysubstance use among Danish 3,4‐methylenedioxymethamphetamine and hallucinogen users: combination patterns and proposed biological bases
Licht, C. L., Christoffersen, M. V., Okholm, M., et al. (2012) · Human Psychopharmacology Clinical and Experimental · doi:10.1002/hup.2234 · Cited by 41 · see citing works
Neuroanatomic specificity and time course of alterations in rat brain serotonergic pathways induced by MDMA (3,4‐methylenedioxymethamphetamine): Assessment using quantitative autoradiography
Battaglia, G., Sharkey, J., Kuhar, M. J., & Souza, E. B. D. (1991) · Synapse · doi:10.1002/syn.890080403 · Cited by 113 · see citing works
Discriminative Stimulus Effects of Psychostimulants and Hallucinogens in S(+)-3,4-Methylenedioxymethamphetamine (MDMA) and R(−)-MDMA Trained Mice
Murnane, K. S., Murai, N., Howell, L. L., & Fantegrossi, W. E. (2009) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.109.156174 · Cited by 34 · see citing works

Authors: Schenk, S., & Highgate, Q.
Affiliations: Victoria University of Wellington (NZ)
Corresponding author: Schenk, Susan
ORCID: Schenk, Susan
Highgate, Quenten
Venue: Journal of Neurochemistry
Publisher: Wiley
Published: 2021-03-25
Volume: 157
Issue: 5
Pages: 1714-1724
ISSN: 0022-3042 (ISSN-L)
1471-4159
DOI: 10.1111/jnc.15348
OpenAlex: W3135595060
Cited by: 48
References: 132
Citations by year: 2026: 5 · 2025: 9 · 2024: 19 · 2023: 6 · 2022: 6 · 2021: 3
FWCI: 1.28
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Journal of Neurochemistry (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: methylenedioxymethamphetamine, MDMA, serotonin, dopamine, drug abuse liability, self-administration, neural adaptation, serotonin receptors, dopamine receptors, substance use disorders, synaptic transmission
MeSH terms: Animals, Dopamine, Humans, Nerve Net, Serotonin, Serotonin Agents, N-Methyl-3,4-methylenedioxyamphetamine, Substance-Related Disorders

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Methylenedioxymethamphetamine (MDMA): Serotonergic and dopaminergic mechanisms related to its use and misuse

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks