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Activation of D 2 ‐like receptors in rat ventral tegmental area inhibits cocaine‐reinstated drug‐seeking behavior
Author(s) -
Xue YueQiang,
Steketee Jeffery D.,
Rebec George V.,
Sun WenLin
Publication year - 2011
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2010.07591.x
Subject(s) - ventral tegmental area , quinpirole , nucleus accumbens , dopamine , eticlopride , neuroscience , dopamine receptor d2 , autoreceptor , conditioned place preference , dopamine receptor , psychology , dopaminergic , agonist , receptor , medicine , sch 23390
Relapse is a hallmark of cocaine addiction. Cocaine‐induced neuroplastic changes in the mesocorticolimbic circuits critically contribute to this phenomenon. Pre‐clinical evidence indicates that relapse to cocaine‐seeking behavior depends on activation of dopamine neurons in the ventral tegmental area. Thus, blocking such activation may inhibit relapse. Because the activity of dopamine neurons is regulated by D 2 ‐like autoreceptors expressed on somatodendritic sites, this study, using the reinstatement model, aimed to determine whether activation of D 2 ‐like receptors in the ventral tegmental area can inhibit cocaine‐induced reinstatement of extinguished cocaine‐seeking behavior. Rats were trained to self‐administer i.v. cocaine (0.25 mg/infusion) under a modified fixed‐ratio 5 schedule. After such behavior was well learned, rats went through extinction training to extinguish cocaine‐seeking behavior. The effect of quinpirole, a selective D 2 ‐like receptor agonist microinjected into the ventral tegmental area, on cocaine‐induced reinstatement was then assessed. Quinpirole (0–3.2 μg/side) dose‐dependently decreased cocaine‐induced reinstatement and such effects were reversed by the selective D 2 ‐like receptor antagonist eticlopride when co‐microinjected with quinpirole into the ventral tegmental area. The effect appeared to be specific to the ventral tegmental area because quinpirole microinjected into the substantia nigra had no effect. Because D 2 ‐like receptors are expressed on rat ventral tegmental area dopamine neurons projecting to the pre‐frontal cortex and nucleus accumbens, our data suggest that these dopamine circuits may play a critical role in cocaine‐induced reinstatement. The role of potential changes in D 2 ‐like receptors and related signaling molecules of dopamine neurons in the vulnerability to relapse was discussed.