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

Publisher: Springer-Verlag Country of Publication: Germany NLM ID: 7608025 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0033-3158 (Print) Linking ISSN: 00333158 NLM ISO Abbreviation: Psychopharmacology (Berl) Subsets: MEDLINE

Original Publication: Berlin, New York, Springer-Verlag.

Dopamine D2 Receptor Antagonists*; Morphine/*administration & dosage ; Nucleus Accumbens/*drug effects ; Sulpiride/*pharmacology ; Ventral Tegmental Area/*drug effects; Animals ; Dopamine Antagonists/pharmacology ; Injections, Intraventricular ; Male ; Mice ; Mice, Inbred BALB C ; Narcotics/administration & dosage ; Nucleus Accumbens/physiology ; Receptors, Dopamine D2/physiology ; Receptors, Dopamine D3 ; Self Administration/methods ; Ventral Tegmental Area/physiology

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.

0 (Dopamine Antagonists)
0 (Dopamine D2 Receptor Antagonists)
0 (Drd3 protein, mouse)
0 (Narcotics)
0 (Receptors, Dopamine D2)
0 (Receptors, Dopamine D3)
76I7G6D29C (Morphine)
7MNE9M8287 (Sulpiride)

Date Created: 20020313 Date Completed: 20020708 Latest Revision: 20141120

20231215

10.1007/s00213-001-0981-2

11889500