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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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.
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.
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.
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.
Both D1 and D2 receptors in the NAc play a prominent, and perhaps cooperative, role in regulating cocaine-taking and cocaine-seeking behaviors.
KeywordsD1 receptor D2 receptor Self-administration Craving Relapse Reinstatement Reward Incentive motivation
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.
- Dias C, Lachize S, Boilet V, Huitelec E, Cador M (2004) Differential effects of dopaminergic agents on locomotor sensitisation and on the reinstatement of cocaine-seeking and food-seeking behaviour. Psychopharmacology 175:105–115Google Scholar
- Hall H, Sallemark M, Jerning E (1986) Effects of remoxipride and some related new substituted salicylamides on rat brain receptors. Acta Pharmacol Toxicol 58:61–70Google Scholar
- Koshikawa N, Kitamura M, Kobayashi M, Cools AR (1996) Contralateral turning elicited by unilateral stimulation of dopamine D2 and D1 receptors in the nucleus accumbens of rats is due to stimulation of these receptors in the shell, but not the core, of this nucleus. Psychopharmacology 126:185–190PubMedCrossRefGoogle Scholar
- Levesque D, Diaz J, Pilon C, Martres MP, Giros B, Souil E, Schott D, Morgat JL, Schwartz JC, Sokoloff P (1992) Identification, characterization, and localization of the dopamine D3 receptor in rat brain using 7-[3H]hydroxy-N,N-di-n-propyl-2-aminotetralin. Proc Natl Acad Sci U S A 89:8155–8159PubMedCrossRefGoogle Scholar
- Park WK, Bari AA, Jey AR, Anderson SM, Spealman RD, Rowlett JK, Pierce RC (2002) Cocaine administered into the medial prefrontal cortex reinstates cocaine-seeking behavior by increasing AMPA receptor-mediated glutamate transmission in the nucleus accumbens. J Neurosci 22:2916–2925PubMedGoogle Scholar
- Paxinos G, Watson C (1998) The rat brain in stereotaxic coordinates, 4th edn. Academic, New YorkGoogle Scholar
- Tiberi M, Jarvie KR, Silvia C, Falardeau P, Gingrich JA, Godinot N, Bertrand L, Yang-Feng TL, Fremeau RT Jr, Caron MG (1991) Cloning, molecular characterization, and chromosomal assignment of a gene encoding a second D1 dopamine receptor subtype: differential expression pattern in rat brain compared with the D1A receptor. Proc Natl Acad Sci U S A 88:7491–7495PubMedCrossRefGoogle Scholar
- Waddington JL, Daly SA (1993) Regulation of unconditioned motor behaviour by D1:D2 interaction. In: Waddington JL (ed) D-1:D-2 dopamine receptor interactions. Academic, London, pp 203–233Google Scholar
- Weiss F, Maldonado-Vlaar CS, Parsons LH, Kerr TM, Smith DL, Ben-Shahar O (2000) Control of cocaine-seeking behavior by drug-associated stimuli in rats: effects on recovery of extinguished operant-responding and extracellular dopamine levels in amygdala and nucleus accumbens. Proc Natl Acad Sci U S A 97:4321–4326CrossRefPubMedGoogle Scholar