Psychopharmacology

, Volume 160, Issue 3, pp 307–317

Differential effects of the dopamine D2/D3 receptor antagonist sulpiride on self-administration of morphine into the ventral tegmental area or the nucleus accumbens

Authors

  • Vincent David
    • Laboratoire de Neurosciences Cognitives, CNRS UMR 5106, Université de Bordeaux I, Avenue des facultés, 33405 Talence Cedex, France
  • Thomas P. Durkin
    • Laboratoire de Neurosciences Cognitives, CNRS UMR 5106, Université de Bordeaux I, Avenue des facultés, 33405 Talence Cedex, France
  • Pierre Cazala
    • Laboratoire de Neurosciences Cognitives, CNRS UMR 5106, Université de Bordeaux I, Avenue des facultés, 33405 Talence Cedex, France
Original Investigation

DOI: 10.1007/s00213-001-0981-2

Cite this article as:
David, V., Durkin, T.P. & Cazala, P. Psychopharmacology (2002) 160: 307. doi:10.1007/s00213-001-0981-2

Abstract.

Rationale: 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. Conclusion: 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.

Intracranial self-administration Morphine Dopamine D2 and D3 receptors Ventral tegmental area Nucleus accumbens Mouse
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© Springer-Verlag 2002