title: Modification of 5-methoxy-N,N-dimethyltryptamine-induced hyperactivity by monoamine oxidase A inhibitor harmaline in mice and the underlying serotonergic mechanisms.
abstract: BACKGROUND
  5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and harmaline are indolealkylamine (IAA) drugs often abused together. Our recent studies have revealed the significant effects of co-administered harmaline, a monoamine oxidase inhibitor (MAOI), on 5-MeO-DMT pharmacokinetics and thermoregulation. This study was to delineate the impact of harmaline and 5-MeO-DMT on home-cage activity in mouse models, as well as the contribution of serotonin (5-HT) receptors.
  
  
  METHODS
  Home-cage activities of individual animals were monitored automatically in the home cages following implantation of telemetry transmitters and administration of various doses of IAA drugs and 5-HT receptor antagonists. Area under the effect curve (AUEC) of mouse activity values were calculated by trapezoidal rule.
  
  
  RESULTS
  High dose of harmaline (15mg/kg, ip) alone caused an early-phase (0-45min) hypoactivity in mice that was fully attenuated by 5-HT1A receptor antagonist WAY-100635, whereas a late-phase (45-180min) hyperactivity that was reduced by 5-HT2A receptor antagonist MDL-100907. 5-MeO-DMT (10 and 20mg/kg, ip) alone induced biphasic effects, an early-phase (0-45min) hypoactivity that was completely attenuated by WAY-100635, and a late-phase (45-180min) hyperactivity that was fully suppressed by MDL-100907. Interestingly, co-administration of MAOI harmaline (2-15mg/kg) with a subthreshold dose of 5-MeO-DMT (2mg/kg) induced excessive hyperactivities at late phase (45-180min) that could be abolished by either WAY-100635 or MDL-100907.
  
  
  CONCLUSIONS
  Co-administration of MAOI with 5-MeO-DMT provokes excessive late-phase hyperactivity, which involves the activation of both 5-HT1A and 5-HT2A receptors.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, USA.
authors.forename: Xi-Ling
authors.initials: XL
authors.lastname: Jiang
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, USA.
authors.forename: Hong-Wu
authors.initials: HW
authors.lastname: Shen
authors.affiliation: Department of Biochemistry & Molecular Medicine, UC Davis School of Medicine, Sacramento, CA, USA. Electronic address: aimyu@ucdavis.edu.
authors.forename: Ai-Ming
authors.initials: AM
authors.lastname: Yu
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005464:Fluorobenzenes; D006246:Harmaline / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006948:Hyperkinesis / Q000139:chemically induced*; D018476:Hypokinesia / Q000139:chemically induced*; D008297:Male; D008732:Methoxydimethyltryptamines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051379:Mice; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D010880:Piperidines; D011725:Pyridines / Q000494:pharmacology; D058825:Serotonin 5-HT1 Receptor Agonists / Q000494:pharmacology*; D058826:Serotonin 5-HT2 Receptor Agonists / Q000494:pharmacology*
chemical_list: D005464:Fluorobenzenes; D008732:Methoxydimethyltryptamines; D008996:Monoamine Oxidase Inhibitors; D010879:Piperazines; D010880:Piperidines; D011725:Pyridines; D058825:Serotonin 5-HT1 Receptor Agonists; D058826:Serotonin 5-HT2 Receptor Agonists; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D006246:Harmaline; C079049:volinanserin
keywords: 5-HT receptor; 5-MeO-DMT; Activity; Harmaline; MAOI