Psychopharmacology

, Volume 183, Issue 1, pp 41–53 | Cite as

Effects of intranucleus accumbens shell administration of dopamine agonists and antagonists on cocaine-taking and cocaine-seeking behaviors in the rat

  • Ryan K. Bachtell
  • Kimberly Whisler
  • David Karanian
  • David W. Self
Original Investigation

Abstract

Rationale

Dopamine signaling in the nucleus accumbens (NAc) plays an important role in regulating drug-taking and drug-seeking behaviors, but the role of D1- and D2-like receptors in this regulation remains unclear.

Objectives

Our objective was to study the role of NAc D1- and D2-like receptors in the reinstatement of cocaine-seeking behavior and the regulation of stabilized cocaine intake in rats.

Methods

Using a within-session reinstatement procedure, whereby animals self-administer cocaine (90 min) and extinguish responding (150 min) in a single session, we assessed the ability of NAc microinfusions of the D1 agonist SKF 81297 and the D2 agonist 7-OH-DPAT to reinstate extinguished cocaine seeking. The effects of the D1 antagonist SCH 23390 and the D2 antagonist eticlopride pretreatment on agonist- and cocaine-primed reinstatement were also measured. Similar agonist and antagonist treatments were tested for their ability to modulate stabilized cocaine and sucrose self-administration.

Results

Intra-NAc infusions of either SKF 81297 (0.3–3.0 μg) or 7-OH-DPAT (1.0–10.0 μg) dose-dependently reinstated cocaine seeking with greater efficacy in the medial core than in the shell subregion and at doses that also stimulated locomotor behavior. Intra-NAc shell infusions of SCH 23390 (1.0 μg) and eticlopride (3.0–10.0 μg) blocked cocaine-primed reinstatement (2.0 mg/kg, i.v.) and indiscriminately blocked reinstatement induced by either intra-NAc D1 or D2 agonists. Doses of agonists that triggered reinstatement failed to alter stabilized cocaine intake, whereas doses of antagonists that blocked reinstatement increased cocaine intake in the shell.

Conclusions

Both D1 and D2 receptors in the NAc play a prominent, and perhaps cooperative, role in regulating cocaine-taking and cocaine-seeking behaviors.

Keywords

D1 receptor D2 receptor Self-administration Craving Relapse Reinstatement Reward Incentive motivation 

Notes

Acknowledgements

This work was supported by United States Public Health Services grants DA 10460, DA 08227, and DA 18481 (R.K.B.), and the Wesley Gilliland Professorship in Biomedical Research.

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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Ryan K. Bachtell
    • 1
  • Kimberly Whisler
    • 1
  • David Karanian
    • 1
  • David W. Self
    • 1
  1. 1.Department of PsychiatryUniversity of Texas Southwestern Medical CenterDallasUSA

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