title: Restoration of serotonin neuronal firing following long-term administration of bupropion but not paroxetine in olfactory bulbectomized rats.
abstract: BACKGROUND
  Olfactory bulbectomized rats generally manifest many of the neurochemical, physiological, and behavioral features of major depressive disorder in humans. Another interesting feature of this model is that it responds to chronic but not acute antidepressant treatments, including selective serotonin reuptake inhibitors. The purpose of the present study was first to characterize the firing activity of dorsal raphe serotonin neurons in olfactory bulbectomized rats and then examine the effects of 2 antidepressants, bupropion and paroxetine.
  
  
  METHODS
  Olfactory bulbectomy was performed by aspirating olfactory bulbs in anesthetized rats. Vehicle and drugs were delivered for 2 and 14 days via subcutaneously implanted minipumps. In vivo electrophysiological recordings were carried out in male anesthetized Sprague-Dawley rats.
  
  
  RESULTS
  Following ablation of olfactory bulbs, the firing rate of serotonin neurons was decreased by 36%, leaving those of norepinephrine and dopamine neurons unchanged. In olfactory bulbectomized rats, bupropion (30 mg/kg/d) restored the firing rate of serotonin neurons to the control level following 2- and 14-day administration and also induced an increase in the tonic activation of serotonin(1A) receptors; paroxetine (10 mg/kg/d) did not result in a return to normal of the attenuated firing of serotonin neurons in olfactory bulbectomized rats. In the hippocampus, although at a higher dose of WAY 100635 than that required in bupropion-treated animals, paroxetine administration also resulted in an increase in the tonic activation of serotonin(1A) receptors.
  
  
  CONCLUSIONS
  The present results indicate that unlike paroxetine, bupropion administration normalized serotonin neuronal activity and increased tonic activation of the serotonin(1A) receptors in hippocampus.
authors.affiliation: University of Ottawa Institute of Mental Health Research, Ottawa, ON, Canada. mostafa.elmansari@theroyal.ca.
authors.forename: Mostafa
authors.initials: M
authors.lastname: El Mansari
authors.affiliation: University of Ottawa Institute of Mental Health Research, Ottawa, ON, Canada.
authors.forename: Stella
authors.initials: S
authors.lastname: Manta
authors.affiliation: University of Ottawa Institute of Mental Health Research, Ottawa, ON, Canada.
authors.forename: Chris
authors.initials: C
authors.lastname: Oosterhof
authors.affiliation: University of Ottawa Institute of Mental Health Research, Ottawa, ON, Canada.
authors.forename: Kareem S
authors.initials: KS
authors.lastname: El Iskandrani
authors.affiliation: University of Ottawa Institute of Mental Health Research, Ottawa, ON, Canada.
authors.forename: Franck
authors.initials: F
authors.lastname: Chenu
authors.affiliation: University of Ottawa Institute of Mental Health Research, Ottawa, ON, Canada.
authors.forename: Stacey
authors.initials: S
authors.lastname: Shim
authors.affiliation: University of Ottawa Institute of Mental Health Research, Ottawa, ON, Canada.
authors.forename: Pierre
authors.initials: P
authors.lastname: Blier
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D016642:Bupropion / Q000494:pharmacology*; D056654:CA3 Region, Hippocampal / Q000187:drug effects / Q000503:physiopathology; D003865:Major Depressive Disorder; D004195:Disease Models, Animal; D065847:Dorsal Raphe Nucleus / Q000187:drug effects* / Q000503:physiopathology; D008125:Locus Coeruleus / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D009830:Olfactory Bulb / Q000503:physiopathology*; D017374:Paroxetine / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects / Q000503:physiopathology; D011725:Pyridines / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D059326:Serotonergic Neurons / Q000187:drug effects* / Q000502:physiology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000502:physiology
chemical_list: D018687:Antidepressive Agents, Second-Generation; D010879:Piperazines; D011725:Pyridines; D012702:Serotonin Antagonists; D016642:Bupropion; D044282:Receptor, Serotonin, 5-HT1A; D017374:Paroxetine; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
keywords: bupropion; electrophysiology; olfactory bulbectomy; paroxetine; serotonin