title: Blocking alpha2A adrenoceptors, but not dopamine receptors, augments bupropion-induced hypophagia in rats.
abstract: OBJECTIVE
  Anti-obesity drugs have adverse effects which limit their use, creating a need for novel anti-obesity compounds. We studied effects of dopamine (DA) and norepinephrine (NE) reuptake inhibitor bupropion (BUP), alone and after blocking α1- or α2-adrenoceptors (AR), D1/5, D2/3, or D4 receptors, to determine which receptors act downstream of BUP.
  
  
  METHODS
  Effects on caloric intake, meal patterning and locomotion were assessed, using an automated weighing system and telemetry in male rats with 18-h access to Western Human style diet.
  
  
  RESULTS
  BUP (30 mg/kg) induced hypophagia by reducing meal size and postponing meal initiation. WB4101 (α1-AR; 2 mg/kg) and imiloxan (α2B-AR; 5 mg/kg) attenuated BUP's effect on meal size, while WB4101 and BRL 44408 (α2A/D-AR; 2 mg/kg) counteracted effect on meal initiation. Atipamezole (α2-AR; 1 mg/kg) and imiloxan further postponed initiation of meals. SKF 83566 (D1/5; 0.3 mg/kg), raclopride (D2/3; 0.5 mg/kg) and to a lesser extent FAUC 213 (D4; 0.5 mg/kg), attenuated BUP-induced hypophagia. BUP stimulated locomotion, which was blocked by all antagonists, except FAUC 213 or BRL 44408.
  
  
  CONCLUSIONS
  Alpha1-, α2A/D- and α2B-ARs, and DA receptors underlie BUP's effects on size and initiation of meals, while blocking pre-synaptic α2-ARs enhanced BUP-induced hypophagia. An inverse agonist of (pre-synaptic) α2A-ARs could enhance BUP-induced anorexia and treat eating disorders and obesity.
authors.affiliation: Rudolf Magnus Institute of Neuroscience, Department of Neuroscience and Pharmacology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Sanna K
authors.initials: SK
authors.lastname: Janhunen
authors.forename: Susanne E
authors.initials: SE
authors.lastname: la Fleur
authors.forename: Roger A H
authors.initials: RA
authors.lastname: Adan
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology*; D016642:Bupropion / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects*; D002149:Energy Intake / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D054833:Isoindoles / Q000494:pharmacology; D008124:Locomotion / Q000187:drug effects; D008297:Male; D062407:Meals / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects* / Q000378:metabolism; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism
chemical_list: D000317:Adrenergic alpha-Antagonists; D019440:Anti-Obesity Agents; D007093:Imidazoles; D054833:Isoindoles; D018341:Receptors, Adrenergic, alpha-2; D011954:Receptors, Dopamine; D016642:Bupropion; C050701:atipamezole; C072125:BRL 44408; C044484:Imiloxan