PMID- 31729537
OWN - NLM
STAT- MEDLINE
DCOM- 20200804
LR  - 20210201
IS  - 1432-2072 (Electronic)
IS  - 0033-3158 (Print)
IS  - 0033-3158 (Linking)
VI  - 237
IP  - 2
DP  - 2020 Feb
TI  - Locomotor effects of 3,4-methylenedioxymethamphetamine (MDMA) and its deuterated 
      form in mice: psychostimulant effects, stereotypy, and sensitization.
PG  - 431-442
LID - 10.1007/s00213-019-05380-3 [doi]
AB  - RATIONALE: There is a renewed interest in the use of 
      3,4-methylenedioxymethamphetamine (MDMA) for treating psychiatric conditions. 
      Although MDMA has entered phase II clinical trials and shows promise as an 
      adjunct treatment, there is an extensive literature detailing the potential 
      neurotoxicity and adverse neurobehavioral effects associated with MDMA use. 
      Previous research indicates that the adverse effects of MDMA may be due to its 
      metabolism into reactive catechols that can enter the brain and serve directly as 
      neurotoxicants. One approach to mitigate MDMA's potential for adverse effects is 
      to reduce O-demethylation by deuterating the methylenedioxy ring of MDMA. There 
      are no studies that have evaluated the effects of deuterating MDMA on behavioral 
      outcomes. OBJECTIVES: The purpose of the present study was to assess the 
      motor-stimulant effects of deuterated MDMA (d2-MDMA) and compare them to MDMA in 
      male mice. METHODS: Two experiments were performed to quantify mouse locomotor 
      activity and to vary the drug administration regimen (single bolus administration 
      or cumulative administration). RESULTS: The results of Experiments 1 and 2 
      indicate that d2-MDMA is less effective at eliciting horizontal locomotion than 
      MDMA; however, the differences between the compounds diminish as the number of 
      cumulative administrations increase. Both d2-MDMA and MDMA can elicit sensitized 
      responses, and these effects cross-sensitize to the prototypical drug of abuse 
      methamphetamine. Thus, d2-MDMA functions as a locomotor stimulant similar to 
      MDMA, but, depending on the dosing regimen, may be less susceptible to inducing 
      sensitization to stereotyped movements. CONCLUSIONS: These findings indicate that 
      d2-MDMA is behaviorally active and produces locomotor effects that are similar to 
      MDMA, which warrant additional assessments of d2-MDMA's behavioral and 
      physiological effects to determine the conditions under which this compound may 
      serve as a relatively safer alternative to MDMA for clinical use.
FAU - Berquist, Michael D
AU  - Berquist MD
AD  - Department of Pharmacology and Toxicology, College of Medicine, University of 
      Arkansas for Medical Sciences, 4301 W. Markham #611, Little Rock, AR, 72205, USA.
FAU - Leth-Petersen, Sebastian
AU  - Leth-Petersen S
AD  - Department of Drug Design and Pharmacology, Faculty of Health and Medical 
      Sciences, University of Copenhagen, Universitetsparken 2, 2100, Kobenhavn O, 
      Denmark.
FAU - Kristensen, Jesper Langgaard
AU  - Kristensen JL
AD  - Department of Drug Design and Pharmacology, Faculty of Health and Medical 
      Sciences, University of Copenhagen, Universitetsparken 2, 2100, Kobenhavn O, 
      Denmark.
FAU - Fantegrossi, William E
AU  - Fantegrossi WE
AD  - Department of Pharmacology and Toxicology, College of Medicine, University of 
      Arkansas for Medical Sciences, 4301 W. Markham #611, Little Rock, AR, 72205, USA. 
      WEFantegrossi@uams.edu.
LA  - eng
GR  - P30 GM110702/GM/NIGMS NIH HHS/United States
GR  - R01 DA039195/DA/NIDA NIH HHS/United States
GR  - HHSF223201610079C/DEA/FDA/
GR  - DA022981/NH/NIH HHS/United States
GR  - GM110702/NH/NIH HHS/United States
GR  - T32 DA022981/DA/NIDA NIH HHS/United States
PT  - Journal Article
DEP - 20191115
PL  - Germany
TA  - Psychopharmacology (Berl)
JT  - Psychopharmacology
JID - 7608025
RN  - 0 (Adrenergic Uptake Inhibitors)
RN  - 0 (Central Nervous System Stimulants)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Adrenergic Uptake Inhibitors/chemistry/pharmacology
MH  - Animals
MH  - Central Nervous System Stimulants/chemistry/*pharmacology
MH  - Locomotion/*drug effects/physiology
MH  - Male
MH  - Mice
MH  - N-Methyl-3,4-methylenedioxyamphetamine/chemistry/*pharmacology
MH  - Stereotyped Behavior/*drug effects/physiology
PMC - PMC7388080
MID - NIHMS1543349
OTO - NOTNLM
OT  - 3,4-Methylenedioxymethamphetamine
OT  - Cross-sensitization
OT  - Cumulative administration
OT  - Deuterium substitution
OT  - Locomotor activity
OT  - MDMA
OT  - Methamphetamine
OT  - Sensitization
OT  - Stereotypy
COIS- Conflict of interest MDB, SLP, JLK, and WEF declare that they have no conflict of 
      interest. Conflict of interest: None
EDAT- 2019/11/16 06:00
MHDA- 2020/08/05 06:00
PMCR- 2021/02/01
CRDT- 2019/11/16 06:00
PHST- 2019/05/23 00:00 [received]
PHST- 2019/10/16 00:00 [accepted]
PHST- 2019/11/16 06:00 [pubmed]
PHST- 2020/08/05 06:00 [medline]
PHST- 2019/11/16 06:00 [entrez]
PHST- 2021/02/01 00:00 [pmc-release]
AID - 10.1007/s00213-019-05380-3 [pii]
AID - 10.1007/s00213-019-05380-3 [doi]
PST - ppublish
SO  - Psychopharmacology (Berl). 2020 Feb;237(2):431-442. doi: 
      10.1007/s00213-019-05380-3. Epub 2019 Nov 15.