PMID- 27318987 OWN - NLM STAT- MEDLINE DCOM- 20171211 LR - 20231213 IS - 1432-2072 (Electronic) IS - 0033-3158 (Linking) VI - 233 IP - 15-16 DP - 2016 Aug TI - Abuse potential of methylenedioxymethamphetamine (MDMA) and its derivatives in zebrafish: role of serotonin 5HT2-type receptors. PG - 3031-9 LID - 10.1007/s00213-016-4352-4 [doi] AB - RATIONALE: The synthetic phenethylamines are recreational drugs known to produce psychostimulant effects. However, their abuse potential has not been widely studied. OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. FAU - Ponzoni, Luisa AU - Ponzoni L AD - Department of Medical Biotechnology and Translational Medicine (BIOMETRA), Universita degli Studi di Milano, Milan, Italy. FAU - Braida, Daniela AU - Braida D AD - Department of Medical Biotechnology and Translational Medicine (BIOMETRA), Universita degli Studi di Milano, Milan, Italy. FAU - Sala, Mariaelvina AU - Sala M AD - Department of Medical Biotechnology and Translational Medicine (BIOMETRA), Universita degli Studi di Milano, Milan, Italy. mariaelvina.sala@unimi.it. AD - Institute of Neuroscience, Consiglio Nazionale delle Ricerche (CNR), Milan, Italy. mariaelvina.sala@unimi.it. AD - Institute of Neuroscience, Consiglio Nazionale delle Ricerche, and Department of Medical Biotechnology and Translational Medicine (BIOMETRA), Universita degli Studi di Milano, Via Vanvitelli 32, 20129, Milan, Italy. mariaelvina.sala@unimi.it. LA - eng PT - Journal Article DEP - 20160618 PL - Germany TA - Psychopharmacology (Berl) JT - Psychopharmacology JID - 7608025 RN - 0 (Amphetamines) RN - 0 (Hallucinogens) RN - 0 (Receptors, Serotonin, 5-HT2) RN - 0 (Serotonin 5-HT2 Receptor Antagonists) RN - 0 (Serotonin Receptor Agonists) RN - 145TFV465S (Ritanserin) RN - 15588-95-1 (DOM 2,5-Dimethoxy-4-Methylamphetamine) RN - 32156-26-6 (2,5-dimethoxy-4-bromoamphetamine) RN - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine) RN - OVB8F8P39Q (4-methoxyamphetamine) SB - IM EIN - Psychopharmacology (Berl). 2016 Dec;233(23-24):4011. Daniela, Braida [corrected to Braida, Daniela]. PMID: 27665759 MH - DOM 2,5-Dimethoxy-4-Methylamphetamine/*analogs & derivatives/pharmacology MH - Amphetamines/*pharmacology MH - Animals MH - Behavior, Animal/*drug effects MH - Conditioning, Psychological/drug effects MH - Female MH - Hallucinogens/*pharmacology MH - Male MH - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology MH - Receptors, Serotonin, 5-HT2/*metabolism MH - Reinforcement, Psychology MH - Reward MH - Ritanserin/pharmacology MH - Serotonin 5-HT2 Receptor Antagonists/pharmacology MH - Serotonin Receptor Agonists/*pharmacology MH - Zebrafish OTO - NOTNLM OT - *Conditioned place preference OT - *DOB OT - *Hallucinogens OT - *PMA OT - *Phenethylamines OT - *Trance-like EDAT- 2016/06/20 06:00 MHDA- 2017/12/12 06:00 CRDT- 2016/06/20 06:00 PHST- 2016/02/19 00:00 [received] PHST- 2016/05/31 00:00 [accepted] PHST- 2016/06/20 06:00 [entrez] PHST- 2016/06/20 06:00 [pubmed] PHST- 2017/12/12 06:00 [medline] AID - 10.1007/s00213-016-4352-4 [pii] AID - 10.1007/s00213-016-4352-4 [doi] PST - ppublish SO - Psychopharmacology (Berl). 2016 Aug;233(15-16):3031-9. doi: 10.1007/s00213-016-4352-4. Epub 2016 Jun 18.