title: Enhancement of serotonergic and noradrenergic neurotransmission in the rat hippocampus by sustained administration of bupropion.
abstract: BACKGROUND
  Previous studies reported that bupropion, an effective antidepressant, exerts modulatory actions on serotonin (5-HT) and norepinephrine (NE) neurons.
  
  
  OBJECTIVE
  This study examined effects of bupropion administration on 5-HT and NE neurotransmission in hippocampus.
  
  
  METHODS
  Electrophysiological recordings were obtained from anesthetized Sprague-Dawley rats. Subcutaneously implanted minipumps delivered saline or bupropion (30 mg/kg/day) for 2 and 14 days.
  
  
  RESULTS
  Although sustained bupropion administration did not alter the sensitivity of 5-HT(1A) and α₂-adrenergic receptors, the tonic activation of postsynaptic 5-HT(1A) receptors by endogenous 5-HT was enhanced in 14-day bupropion-treated rats to a greater extent than in the 2-day and control rats, as revealed by the greater disinhibitory action of the 5-HT(1A) antagonist WAY-100635 on hippocampus pyramidal neurons. The function of terminal 5-HT(1B) autoreceptors was not changed as determined by the unaltered effectiveness of different frequencies of stimulation of the ascending 5-HT fibers. The function of α₂-adrenergic receptors on 5-HT terminals was, however, diminished, as indicated by the lesser effect of the α₂-adrenoceptor agonist clonidine. Tonic activation of postsynaptic α₂- and α₁-adrenoceptors by endogenous NE was also increased in 14-day bupropion-treated rats, as indicated by the greater effect of the α₂- and α₁-adrenoceptor antagonists idazoxan and prazosin, respectively, on pyramidal firing. The function of terminal α₂-adrenergic autoreceptors was attenuated since increasing frequency of stimulation of the ascending NE pathway produced a lesser degree of suppression of pyramidal neurons in rats administered bupropion than the control.
  
  
  CONCLUSIONS
  Enhancement of 5-HT and NE transmissions in hippocampus by prolonged bupropion may account for its effectiveness in major depression.
authors: Institute of Mental Health Research, University of Ottawa, Room 6411, 1145 Carling Avenue, Ottawa, K1Z7K4 ON, Canada.
authors: Ramez
authors: R
authors: Ghanbari
authors: Mostafa
authors: M
authors: El Mansari
authors: Pierre
authors: P
authors: Blier
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage / Q000494:pharmacology*; D016642:Bupropion / Q000008:administration & dosage / Q000494:pharmacology*; D056654:CA3 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism; D004558:Electric Stimulation; D015918:Infusion Pumps, Implantable; D007478:Iontophoresis; D008297:Male; D009474:Neurons; D009638:Norepinephrine / Q000378:metabolism*; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D018687:Antidepressive Agents, Second-Generation; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D016642:Bupropion; D044282:Receptor, Serotonin, 5-HT1A; D009638:Norepinephrine