title: The modulatory action of harmane on serotonergic neurotransmission in rat brain.
abstract: The naturally occurring β-carboline, harmane, has been implicated in various physiological and psychological conditions. Some of these effects are attributed to its interaction with monoaminergic systems. Previous literature indicates that certain β-carbolines including harmane modulate central monoamine levels partly through monoamine oxidase (MAO) inhibition. However, this is not always the case and thus additional mechanisms may be involved. This study set to assess the potential modulatory role of harmane on the basal or K(+) stimulated release of preloaded radiolabelled noradrenaline (NA), dopamine (DA) and serotonin (5-HT) in rat brain cortex in vitro in the presence of the MAO inhibitor pargyline. Harmane displayed an overt elevation in K(+) -evoked [(3)H]5-HT release; whilst little and no effect was reported with [(3)H]DA and [(3)H]NA respectively. The effect of harmane on [(3)H]5-HT efflux was partially compensated in K(+)-free medium. Further analyses demonstrated that removal of Ca(2+) ions and addition of 1.2mM EGTA did not alter the action of harmane on [(3)H]5-HT release from rat brain cortex. The precise mechanism of action however remains unclear but is unlikely to reflect an involvement of MAO inhibition. The current finding aids our understanding on the modulatory action of harmane on monoamine levels and could potentially be of therapeutic use in psychiatric conditions such as depression and anxiety.
authors.affiliation: Psychopharmacology Unit, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol, BS1 3NY, UK; General Education Department, American University of the Middle East, P.O. BOX 220 Dasman, 15453 Kuwait. Electronic address: Haya.Abu-Ghazaleh@aum.edu.kw.
authors.forename: Haya
authors.initials: H
authors.lastname: Abu Ghazaleh
authors.affiliation: Pharmacology Department, University of Alberta, Medical Sciences Building, Edmonton, Alberta, T6G 2H7, Canada.
authors.forename: Maggie D
authors.initials: MD
authors.lastname: Lalies
authors.affiliation: Centre for Neuropsychopharmacology, Imperial College London, Burlington Danes Building, London, W12 0NN, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Nutt
authors.affiliation: Pharmacology Department, University of Alberta, Medical Sciences Building, Edmonton, Alberta, T6G 2H7, Canada.
authors.forename: Alan L
authors.initials: AL
authors.lastname: Hudson
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D065096:Calcium Chelating Agents / Q000494:pharmacology; D002243:Carbolines / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000502:physiology; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000494:pharmacology; D006247:Harmine / Q000031:analogs & derivatives* / Q000494:pharmacology; D007477:Ions / Q000378:metabolism; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism; D010293:Pargyline / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D018490:Serotonin Agents / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D046509:Tissue Culture Techniques
chemical_list: D065096:Calcium Chelating Agents; D002243:Carbolines; D007477:Ions; D008996:Monoamine Oxidase Inhibitors; D018490:Serotonin Agents; D012701:Serotonin; D006247:Harmine; C045323:harmalan; D004533:Egtazic Acid; C005010:harman; C010262:norharman; D010293:Pargyline; D011188:Potassium; D002118:Calcium; D004298:Dopamine; D009638:Norepinephrine
keywords: 5-HT release; Harmane; Monoamine; Neurotransmitter; β-carboline