Differential effects of the dopamine D2/D3 receptor antagonist sulpiride on self-administration of morphine into the ventral tegmental area or the nucleus accumbens.
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.
David
Vincent
V
Laboratoire de Neurosciences Cognitives, CNRS UMR 5106, Université de Bordeaux I, Avenue des facultés, 33405 Talence Cedex, France.
Durkin
Thomas P
TP
Cazala
Pierre
P
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
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