Activation of D2-like receptors in rat ventral tegmental area inhibits cocaine-reinstated drug-seeking behavior

Yueqiang Xue, Jeffery Steketee, George V. Rebec, Wen Lin Sun

Research output: Contribution to journalArticle

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Abstract

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 D2-like autoreceptors expressed on somatodendritic sites, this study, using the reinstatement model, aimed to determine whether activation of D2-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 (0.25mg/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 D2-like receptor agonist microinjected into the ventral tegmental area, on cocaine-induced reinstatement was then assessed. Quinpirole (0-3.2μg/side) dose-dependently decreased cocaine-induced reinstatement and such effects were reversed by the selective D2-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 D2-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 D2-like receptors and related signaling molecules of dopamine neurons in the vulnerability to relapse was discussed.

Original languageEnglish (US)
Pages (from-to)1291-1298
Number of pages8
JournalEuropean Journal of Neuroscience
Volume33
Issue number7
DOIs
StatePublished - Apr 1 2011

Fingerprint

Drug-Seeking Behavior
Ventral Tegmental Area
Cocaine
Quinpirole
Dopaminergic Neurons
Recurrence
eticlopride
Autoreceptors
Cocaine-Related Disorders
Nucleus Accumbens
Frontal Lobe
Substantia Nigra
Dopamine
Appointments and Schedules

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Activation of D2-like receptors in rat ventral tegmental area inhibits cocaine-reinstated drug-seeking behavior. / Xue, Yueqiang; Steketee, Jeffery; Rebec, George V.; Sun, Wen Lin.

In: European Journal of Neuroscience, Vol. 33, No. 7, 01.04.2011, p. 1291-1298.

Research output: Contribution to journalArticle

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