Tags

Type your tag names separated by a space and hit enter

Activation of D₂-like receptors in rat ventral tegmental area inhibits cocaine-reinstated drug-seeking behavior.
Eur J Neurosci 2011; 33(7):1291-8EJ

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 (0.25 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 D₂-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 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.

Authors+Show Affiliations

Department of Pharmacology, University of Tennessee Health Science Center, Memphis, TN 38163, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

21261759

Citation

Xue, Yueqiang, et al. "Activation of D₂-like Receptors in Rat Ventral Tegmental Area Inhibits Cocaine-reinstated Drug-seeking Behavior." The European Journal of Neuroscience, vol. 33, no. 7, 2011, pp. 1291-8.
Xue Y, Steketee JD, Rebec GV, et al. Activation of D₂-like receptors in rat ventral tegmental area inhibits cocaine-reinstated drug-seeking behavior. Eur J Neurosci. 2011;33(7):1291-8.
Xue, Y., Steketee, J. D., Rebec, G. V., & Sun, W. (2011). Activation of D₂-like receptors in rat ventral tegmental area inhibits cocaine-reinstated drug-seeking behavior. The European Journal of Neuroscience, 33(7), pp. 1291-8. doi:10.1111/j.1460-9568.2010.07591.x.
Xue Y, et al. Activation of D₂-like Receptors in Rat Ventral Tegmental Area Inhibits Cocaine-reinstated Drug-seeking Behavior. Eur J Neurosci. 2011;33(7):1291-8. PubMed PMID: 21261759.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of D₂-like receptors in rat ventral tegmental area inhibits cocaine-reinstated drug-seeking behavior. AU - Xue,Yueqiang, AU - Steketee,Jeffery D, AU - Rebec,George V, AU - Sun,Wenlin, Y1 - 2011/01/24/ PY - 2011/1/26/entrez PY - 2011/1/26/pubmed PY - 2011/7/19/medline SP - 1291 EP - 8 JF - The European journal of neuroscience JO - Eur. J. Neurosci. VL - 33 IS - 7 N2 - 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 (0.25 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 D₂-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 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. SN - 1460-9568 UR - https://www.unboundmedicine.com/medline/citation/21261759/Activation_of_D₂_like_receptors_in_rat_ventral_tegmental_area_inhibits_cocaine_reinstated_drug_seeking_behavior_ L2 - https://doi.org/10.1111/j.1460-9568.2010.07591.x DB - PRIME DP - Unbound Medicine ER -