Harmane inhibits serotonergic dorsal raphe neurons in the rat.
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.
Touiki
Khalid
K
Laboratoire de Psychopharmacologie, Centre Hospitalier Paul Guiraud, 54 avenue de la République, Villejuif, 94806, France.
Rat
Pascal
P
Molimard
Robert
R
Chait
Abderrahman
A
de Beaurepaire
Renaud
R
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
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