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

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Abstract
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. Our objective was to study the role of NAc D(1)- and D(2)-like receptors in the reinstatement of cocaine-seeking behavior and the regulation of stabilized cocaine intake in rats. 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. Intra-NAc infusions of either SKF 81297 (0.3-3.0 microg) or 7-OH-DPAT (1.0-10.0 microg) 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 microg) and eticlopride (3.0-10.0 microg) blocked cocaine-primed reinstatement (2.0 mg/kg, i.v.) and indiscriminately blocked reinstatement induced by either intra-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. 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.