Double dissociation between actions of dopamine D1 and D2 receptors of the ventral and dorsolateral striatum to produce reinstatement of cocaine seeking behavior

NEUROPHARMACOLOGY

卷:172

Article

Campos, Renan Costa^1,2,3  Dias, Carine¹  Darlot, Florence^1,2  Cador, Martine^1,2 

[1] Univ Bordeaux, F-33076 Bordeaux, France

[2] CNRS, Inst Neurosci Cognit & Integrat Aquitaine, UMR 5287, Bordeaux, France

[3] CNRS, Inst Pharmacol Mol & Cellulaire, UMR 7275, Valbonne, France

关键词: Self-administration;    Striatum;    Dopamine;    Reinstatement;    Cocaine;    Addiction;   

DOI  :  10.1016/j.neuropharm.2020.108113

来源: Elsevier

【 摘 要 】

One of the hallmarks of addiction is the enduring vulnerability to relapse. Following repeated use, cocaine (COC) induces neuroadaptations within the dopamine (DA) system, arguably underlying several aspects of COC-seeking behavior. Peripheral stimulation of D2, but not D1, receptors induces relapse. However, where in the brain these effects occur is still matter of debate. The D1 and D2 receptors (D1R; D2R) are highly expressed in the nucleus accumbens (NAcc) and the dorsolateral striatum (DLS), but their specific involvement in the reinstatement of COC-seeking remains elusive. We assessed the reinstating effects of intracerebral infusions of agonists of D1R (SKF82958) or D2R (quinelorane) within the NAcc or DLS of rats after extinction of COC self-administration (COC SA). To assess whether we could block peripheral D2 agonist (quinelorane) induced reinstatement, we simultaneously infused either a D1R (SCH23390) or a D2R (raclopride) antagonist within the NAcc or DLS. When infused into the NAcc, but not into the DLS, SKF82958 induced reinstatement of COC-seeking; conversely, quinelorane had no effect when injected into the NAcc, but induced reinstatement when infused into the DLS while the D1R agonist has no effect. While administration of raclopride into the NAcc or DLS impedes the reinstating effect of a systemic quinelorane injection, the infusion of SCH23390 into the NAcc or DLS surprisingly, blocks the reinstatement induced by the peripheral D2R stimulation. Our results point to a double dissociation between D1R and D2R of the NAcc and DLS, highlighting their complex interactions within both structures, in the reinstatement of COC-seeking behavior.

【 授权许可】

Free