Abuse potential of methylenedioxymethamphetamine (MDMA) and its derivatives in zebrafish: role of serotonin 5HT2-type receptors.
Luisa Ponzoni, Daniela Braida, Mariaelvina Sala
Psychopharmacology August 2016 DOI: 10.1007/s00213-016-4352-4 (opens in new tab)
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Study at a glance
AI-extracted from the abstract| Characteristics | Controlled experimental animal study Peer reviewed |
|---|---|
| Population | Zebrafish (Danio rerio) |
| Interventions | DOB (2 Ritanserin |
| Dose | DOB 0.1-20 mg/kg; PMA 0.0005-2 mg/kg; MDMA 0.5-160 mg/kg; ritanserin 0.025-2.5 mg/kg; maximal effective doses: DOB 2 mg/kg, PMA 0.1 mg/kg, MDMA 160 mg/kg |
| Measures | conditioned place preference (CPP), trance-like hallucinatory behavior |
| Topics | MDMA Serotonin |
| Keywords | Conditioned place preference Dob Hallucinogens Pma Phenethylamines Trance-like |
| Key findings | MDMA, DOB, and PMA all produced conditioned place preference in zebrafish in a biphasic manner, with PMA the most potent; DOB and PMA also induced trance-like hallucinatory behavior, whereas MDMA did not. Ritanserin blocked both effects, which the authors argue indicates involvement of serotonin 5-HT2 receptors. |
Abstract
The synthetic phenethylamines are recreational drugs known to produce psychostimulant effects. However, their abuse potential has not been widely studied. Here, we investigated the rewarding and the hallucinatory effects of 2,5-dimetoxy-4-bromo-amphetamine hydrobromide (DOB) and para-methoxyamphetamine (PMA) in comparison with the classical 3,4-methylenedioxymethamphetamine (MDMA). In addition, the role of serotonin 5-HT2-like receptor on the abovementioned effects was evaluated. Zebrafish were intramuscularly (i.m.) treated with a wide range of doses of DOB (0.1-20 mg/kg), PMA (0.0005-2 mg/kg), or MDMA (0.5-160 mg/kg). Animals were submitted to a conditioned place preference (CPP) task, to investigation of the rewarding properties, and to the evaluation of hallucinatory behavior in terms of appearance of a trance-like behavior. The serotonin 5-HT2 subtype receptor antagonist ritanserin (0.025-2.5 mg/kg) in association with the maximal effective dose of MDMA, DOB, and PMA was given i.m., and the effect on CPP or hallucinatory behavior was evaluated. MDMA and its derivatives exhibited CPP in a biphasic fashion, being PMA the most potent. This effect was accompanied, for DOB (2 mg/kg) and PMA (0.1 mg/kg), by a trance-like hallucinatory behavior. MDMA at a high dose as 160 mg/kg did not induce any hallucinatory behavior. Ritanserin significantly blocked the rewarding and hallucinatory effects suggesting the involvement of serotonin 5HT2 subtype receptor. Collectively, these findings demonstrate for the first time that the rewarding properties of DOB and PMA are accompanied by hallucinatory behavior through a serotonergic system and reinforce zebrafish as an emerging experimental model for screening new hallucinogens.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
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- Acute DOB and PMA Administration Impairs Motor and Sensorimotor Responses in Mice and Causes Hallucinogenic Effects in Adult Zebrafish Brain Sciences August 25, 2020
- The Non-Peptide Arginine-Vasopressin v1a Selective Receptor Antagonist, SR49059, Blocks the Rewarding, Prosocial, and Anxiolytic Effects of 3,4-Methylenedioxymethamphetamine and Its Derivatives in Zebra Fish Frontiers in Psychiatry August 13, 2017
- Repeated administration of the synthetic cannabinoid AKB48 induces serotonergic neuroadaptation in male and female mice: behavioural and immunohistochemical evidence. Neuropharmacology February 1, 2026
- Unveil the toxicity induced on early life stages of zebrafish (Danio rerio) exposed to 3,4-methylenedioxymethamphetamine (MDMA) and its enantiomers. The Science of the total environment December 10, 2024
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