Abuse potential of methylenedioxymethamphetamine (MDMA) and its derivatives in zebrafish: role of serotonin 5HT2-type receptors

Ponzoni, Luisa; Braida, Daniela; Sala, Mariaelvina

doi:10.1007/s00213-016-4352-4

Cited by 10 publications

(8 citation statements)

References 62 publications

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“…The trance-like behavior evoked by PMA showed a biphasic trend. In zebrafish, this pattern has also been observed for other effects induced by DOB and PMA, like pro-social, anxiolytic, and rewarding [ 30 , 76 ]. The observed inverted U-shaped curve is also in line with the findings obtained in other animal models, and in some human studies [ 77 ].…”

Section: Discussionmentioning

confidence: 58%

“…Regarding zebrafish, it is necessary to rely on recent studies conducted by Ponzoni and his colleagues, according to which the effects of DOB and PMA in Conditioned Place Preference (CPP) tests are predictive of the potential abuse of these substances, and its “trance-like” behavior typical of hallucinogenic substances [ 76 ]. Notably, the rewarding and hallucinatory effect was blocked by ritanserin, a serotonin 5-HT2 receptor subtype antagonist, suggesting the involvement of the serotonergic system [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

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Acute DOB and PMA Administration Impairs Motor and Sensorimotor Responses in Mice and Causes Hallucinogenic Effects in Adult Zebrafish

et al. 2020

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The drastic increase in hallucinogenic compounds in illicit drug markets of new psychoactive substances (NPS) is a worldwide threat. Among these, 2, 5-dimetoxy-4-bromo-amphetamine (DOB) and paramethoxyamphetamine (PMA; marketed as “ecstasy”) are frequently purchased on the dark web and consumed for recreational purposes during rave/dance parties. In fact, these two substances seem to induce the same effects as MDMA, which could be due to their structural similarities. According to users, DOB and PMA share the same euphoric effects: increasing of the mental state, increasing sociability and empathy. Users also experienced loss of memory, temporal distortion, and paranoia following the repetition of the same thought. The aim of this study was to investigate the effect of the acute systemic administration of DOB and PMA (0.01–30 mg/kg; i.p.) on motor, sensorimotor (visual, acoustic, and tactile), and startle/PPI responses in CD-1 male mice. Moreover, the pro-psychedelic effect of DOB (0.075–2 mg/kg) and PMA (0.0005–0.5 mg/kg) was investigated by using zebrafish as a model. DOB and PMA administration affected spontaneous locomotion and impaired behaviors and startle/PPI responses in mice. In addition, the two compounds promoted hallucinatory states in zebrafish by reducing the hallucinatory score and swimming activity in hallucinogen-like states.

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Section: Discussionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 99%

Acute DOB and PMA Administration Impairs Motor and Sensorimotor Responses in Mice and Causes Hallucinogenic Effects in Adult Zebrafish

et al. 2020

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“…Figure 1 shows the chemical structures of MDMA, DOB, and PMA (Sigma-Aldrich, St. Louis, MO, USA), which were dissolved in sterile saline at doses of, respectively, 10, 0.5, and 0.1 mg/kg and administered intramuscularly (IM) 5 min before each test. The doses were chosen on the basis of their known ability to maximize the drugs’ rewarding, social, and anxiolytic effects ( 23 , 53 ). Given the unavailability of specific antagonists of zebra fish IT/AVT receptor subtypes and selective OT antagonists, we used (2S)-1-[[(2R,3S)5-chloro-3(2-chlorophenyl)-1-[(3,4-dimethoxyphenyl)sulfonyl]-2,3-dihydro-3hydroxy-1H-indol-2-l]carbonyl]-2-pyrrolidine carboxamide (SR49059; Sigma-Aldrich, St. Louis, MO, USA), the most selective antagonist of human and rat vasopressin V 1a receptors ( 60 ), at doses of 0.01, 0.1, and 1 mg/kg, which are known to block the prosocial effects of IT and AVT in zebra fish ( 62 ).…”

Section: Methodsmentioning

confidence: 99%

“…The recently discovered, dose-dependent rewarding, anxiolytic, and prosocial effects of MDMA, DOB, and PMA on zebra fish ( 23 , 53 ) can be completely blocked by ritanserin, thus suggesting the involvement of 5-HT 2A/C receptors. However, there is growing evidence that the neuropeptide oxytocin (OT) can modulate drug-related reward and may act as a pharmacological treatment of drug dependence ( 54 ).…”

Section: Introductionmentioning

confidence: 97%

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

et al. 2017

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3,4-Methylenedioxymethamphetamine (MDMA) and its derivatives, 2,5-dimethoxy-4-bromo-amphetamine hydrobromide (DOB) and para-methoxyamphetamine (PMA), are recreational drugs whose pharmacological effects have recently been attributed to serotonin 5HT2A/C receptors. However, there is growing evidence that the oxytocin (OT)/vasopressin system can modulate some the effects of MDMA. In this study, MDMA (2.5–10 mg/kg), DOB (0.5 mg/kg), or PMA (0.005, 0.1, or 0.25 mg/kg) were administered intramuscularly to adult zebra fish, alone or in combination with the V1a vasopressin antagonist, SR49059 (0.01–1 ng/kg), before carrying out conditioned place preference (CPP), social preference, novel tank diving, and light–dark tests in order to evaluate subsequent rewarding, social, and emotional-like behavior. The combination of SR49059 and each drug progressively blocked: (1) rewarding behavior as measured by CPP in terms of time spent in drug-paired compartment; (2) prosocial effects measured on the basis of the time spent in the proximity of a nacre fish picture; and (3) anxiolytic effects in terms of the time spent in the upper half of the novel tank and in the white compartment of the tank used for the light–dark test. Antagonism was obtained at SR49059 doses which, when given alone, did not change motor function. In comparison with a control group, receiving vehicle alone, there was a three to five times increase in the brain release of isotocin (the analog of OT in fish) after treatment with the most active doses of MDMA (10 mg/kg), DOB (0.5 mg/kg), and PMA (0.1 mg/kg) as evaluated by means of bioanalytical reversed-phase high-performance liquid chromatography. Taken together, these findings show that the OT/vasopressin system is involved in the rewarding, prosocial, and anxiolytic effects of MDMA, DOB, and PMA in zebra fish and underline the association between this system and the behavioral alterations associated with disorders related to substance abuse.

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“…This system is particularly relevant, because albeit not fully conserved in terms of neuroanatomy and genetics (Herculano & Maximino, ), it is functionally associated with emotional domains across vertebrates and invertebrates (Curran & Chalasani, ; Herculano & Maximino, ; Mohammad et al, ). Zebrafish anxiety‐like behavior is usually affected by serotonin in a receptor‐dependent manner (Herculano & Maximino, ; Maximino, Lima, Costa, Guedes, & Herculano, ; Nowicki, Tran, Muraleetharan, Markovic, & Gerlai, ; Ogawa, Ng, Ramadasan, Nathan, & Parhar, ; Ponzoni, Daniela, & Sala, ). For example, serotonergic psychedelics, such as lysergic acid diethylamide (LSD) (Grossman et al, ), mescaline (Kyzar et al, ) and 3,4‐methylenedioxymethamphetamine (MDMA; Stewart, Riehl, et al, ), evoke anxiolytic‐like effects in zebrafish, increasing top swimming in the NTT and decreasing dark preference in the LDT.…”

Section: Measuring Affective‐like Behavior In Crayfish and Zebrafishmentioning

confidence: 99%

Emotional behavior in aquatic organisms? Lessons from crayfish and zebrafish

Abreu

Maximino

Banha

et al. 2019

J of Neuroscience Research

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Experimental animal models are a valuable tool to study the neurobiology of emotional behavior and mechanisms underlying human affective disorders. Mounting evidence suggests that various aquatic organisms, including both vertebrate (e.g., zebrafish) and invertebrate (e.g., crayfish) species, may be relevant to study animal emotional response and its deficits. Ideally, model organisms of disease should possess considerable genetic and physiological homology to mammals, display robust behavioral and physiological responses to stress, and should be sensitive to a wide range of drugs known to modulate stress and affective behaviors. Here, we summarize recent findings in the field of zebrafish‐ and crayfish‐based tests of stress, anxiety, aggressiveness and social preference, and discuss further perspectives of using these novel model organisms in translational biological psychiatry. Outlining the remaining questions in this field, we also emphasize the need in further development and a wider use of crayfish and zebrafish models to study the pathogenesis of affective disorders.

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Abuse potential of methylenedioxymethamphetamine (MDMA) and its derivatives in zebrafish: role of serotonin 5HT2-type receptors

Abstract: 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.

Cited by 10 publications

References 62 publications

Acute DOB and PMA Administration Impairs Motor and Sensorimotor Responses in Mice and Causes Hallucinogenic Effects in Adult Zebrafish

Acute DOB and PMA Administration Impairs Motor and Sensorimotor Responses in Mice and Causes Hallucinogenic Effects in Adult Zebrafish

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

Emotional behavior in aquatic organisms? Lessons from crayfish and zebrafish

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