title: Harmane inhibits serotonergic dorsal raphe neurons in the rat.
abstract: BACKGROUND
  Harmane and norharmane (two beta-carbolines) are tobacco components or products. The effects of harmane and norharmane on serotonergic raphe neurons remain unknown. Harmane and norharmane are inhibitors of the monoamine oxidases A (MAO-A) and B (MAO-B), respectively.
  
  
  OBJECTIVE
  To study the effects of harmane, norharmane, befloxatone (MAOI-A), and selegiline (MAOI-B) on the firing of serotonergic neurons. To compare the effects of these compounds to those of nicotine (whose inhibitory action on serotonergic neurons has been previously described). The effects of cotinine, a metabolite of nicotine known to interact with serotonergic systems, are also tested.
  
  
  METHODS
  In vivo electrophysiological recordings of serotonergic dorsal raphe neurons in the anaesthetized rat.
  
  
  RESULTS
  Nicotine, harmane, and befloxatone inhibited serotonergic dorsal raphe neurons. The other compounds had no effects. The inhibitory effect of harmane (rapid and long-lasting inhibition) differed from that of nicotine (short and rapidly reversed inhibition) and from that of befloxatone (slow, progressive, and long-lasting inhibition). The inhibitory effects of harmane and befloxatone were reversed by the 5-HT1A antagonist WAY 100 635. Pretreatment of animals with p-chlorophenylalanine abolished the inhibitory effect of befloxatone, but not that of harmane.
  
  
  CONCLUSIONS
  Nicotine, harmane, and befloxatone inhibit the activity of raphe serotonergic neurons. Therefore, at least two tobacco compounds, nicotine and harmane, inhibit the activity of serotonergic neurons. The mechanism by which harmane inhibits serotonergic dorsal raphe neurons is likely unrelated to a MAO-A inhibitory effect.
authors.affiliation: Laboratoire de Psychopharmacologie, Centre Hospitalier Paul Guiraud, 54 avenue de la République, Villejuif, 94806, France.
authors.forename: Khalid
authors.initials: K
authors.lastname: Touiki
authors.forename: Pascal
authors.initials: P
authors.lastname: Rat
authors.forename: Robert
authors.initials: R
authors.lastname: Molimard
authors.forename: Abderrahman
authors.initials: A
authors.lastname: Chait
authors.forename: Renaud
authors.initials: R
authors.lastname: de Beaurepaire
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D002243:Carbolines; D015283:Citalopram / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006247:Harmine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009498:Neurotoxins / Q000494:pharmacology*; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D010080:Oxazoles / Q000494:pharmacology; D010627:Phenethylamines / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011903:Raphe Nuclei / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012642:Selegiline / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology
chemical_list: D002243:Carbolines; D015283:Citalopram; D004791:Enzyme Inhibitors; D006247:Harmine; D009498:Neurotoxins; D009538:Nicotine; D018722:Nicotinic Agonists; D010080:Oxazoles; D010627:Phenethylamines; D010879:Piperazines; D011725:Pyridines; D012642:Selegiline; D012701:Serotonin; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; C024320:4-chlorophenethylamine; C090014:befloxatone; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; C005010:harman; C010262:norharman