title: Differential effects of the dopamine D2/D3 receptor antagonist sulpiride on self-administration of morphine into the ventral tegmental area or the nucleus accumbens.
abstract: BACKGROUND
  The involvement of dopamine neurotransmission in opiate reward remains controversial.
  
  
  OBJECTIVE
  To investigate the dopaminergic basis of opiate reward by comparing the effect of systemic injection of the D2/D3 antagonist sulpiride on morphine self-administration (ICSA) into the ventral tegmental area (VTA) or the nucleus accumbens (NAc)
  
  
  METHODS
  BALB/c mice were unilaterally implanted with a guide cannula 1.5 mm above either the VTA or the NAc. On experimental days, a stainless-steel injection cannula was inserted via the guide cannula, and mice were trained to discriminate the arm of a Y-maze reinforced by intracranial morphine microinjections (6.5 pmol or 65 pmol/50 nl) from the neutral arm (no injection). Following acquisition of morphine ICSA, the dopamine D2/D3 receptor antagonist sulpiride (50 mg/kg, i.p.) was administered 30 min before testing.
  
  
  RESULTS
  Sulpiride produced an extinction of intra-VTA, but not intra-NAC, morphine self-administration. Extinction in VTA subjects was followed by a re-appearance of ICSA, although mice continued to receive sulpiride injections. Extinction was re-induced when the dose of sulpiride was raised to 100 mg/kg, whereas no effect of this dose was detected on intra-NAc self-administration.
  
  
  CONCLUSIONS
  Maintenance of intra-VTA, but not intra-NAc, morphine self-administration depends acutely on D2/D3 receptors. However, the deleterious effect of sulpiride on intra-VTA morphine self-administration is transient. Reappearance of ICSA under neuroleptic treatment in VTA subjects may be related to the sensitization effect of intra-VTA morphine infusions, combined with an upregulation of D2/D3 receptors and alterations of DA metabolism by repeated sulpiride injections.
authors.affiliation: Laboratoire de Neurosciences Cognitives, CNRS UMR 5106, Université de Bordeaux I, Avenue des facultés, 33405 Talence Cedex, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: David
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Durkin
authors.forename: Pierre
authors.initials: P
authors.lastname: Cazala
mesh_terms: D000818:Animals; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009020:Morphine / Q000008:administration & dosage*; D009294:Narcotics / Q000008:administration & dosage; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000502:physiology; D050637:Receptors, Dopamine D3; D012646:Self Administration / Q000379:methods; D013469:Sulpiride / Q000494:pharmacology*; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000502:physiology
chemical_list: D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; C493594:Drd3 protein, mouse; D009294:Narcotics; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D009020:Morphine; D013469:Sulpiride