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

Rationale: Dopamine signaling in the nucleus accumbens (NAc) plays an important role in regulating drug-taking and drug-seeking behaviors, but the role of D-1- and D-2-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 D-1 agonist SKF 81297 and the D-2 agonist 7-OH-DPAT to reinstate extinguished cocaine seeking. The effects of the D-1 antagonist SCH 23390 and the D-2 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: Infra-NAc infusions-of either SKF 81297 (0.3-3.0 mu g) or 7-OH-DPAT (1.0-10.0 mu g) 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. Infra-NAc shell infusions of SCH 23390 (1.0 mu g) and eticlopride (3.0-10.0 mu g) blocked cocaine-primed reinstatement (2.0 mg/kg, i.v.) and indiscriminately blocked reinstatement induced by either infra-NAc D-1 or D-2 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 D-1 and D-2 receptors in the NAc play a prominent, and perhaps cooperative, role in regulating cocaine-taking and cocaine-seeking behaviors.