QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (120) Citing Articles via Google Scholar Google Scholar Articles by Vorel, S. R. Articles by Gardner, E. L. Search for Related Content PubMed PubMed Citation Articles by Vorel, S. R. Articles by Gardner, E. L.

 Previous Article  |  Next Article 

The Journal of Neuroscience, November 1, 2002, 22(21):9595-9603

Dopamine D₃ Receptor Antagonism Inhibits Cocaine-Seeking and Cocaine-Enhanced Brain Reward in Rats

Stanislav R. Vorel^{1, 2}, Charles R. Ashby Jr⁴, Mousumi Paul⁵, Xinhe Liu³, Robert Hayes², Jim J. Hagan⁶, Derek N. Middlemiss⁶, Geoffrey Stemp⁶, and Eliot L. Gardner^{1, 2, 3}

¹ Intramural Research Program, National Institute on Drug Abuse, Baltimore, Maryland 21224, Departments of ² Neuroscience and ³ Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, Bronx, New York 10461, ⁴ Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, Saint John's University, Jamaica, New York 11439, ⁵ Eon Laboratories, Laurelton, New York 11413, and ⁶ Psychiatry Centre of Excellence for Drug Discovery, GlaxoSmithKline, Harlow, Essex CM19 5AW, United Kingdom

The dopamine D₃ receptor is preferentially localized to the mesocorticolimbic dopaminergic system and has been hypothesized to play a role in cocaine addiction. To study the involvement of the D₃ receptor in brain mechanisms and behaviors commonly assumed to be involved in the addicting properties of cocaine, the potent and selective D₃ receptor antagonist trans-N-[4-[2-(6-cyano-1,2,3,4-tetrahydroisoquinolin-2-yl)ethyl] cyclohexyl]-4-quinolininecarboxamide (SB-277011-A) was administered to laboratory rats, and the following measures were assessed: (1) cocaine-enhanced electrical brain-stimulation reward, (2) cocaine-induced conditioned place preference, and (3) cocaine-triggered reinstatement of cocaine seeking behavior. Systemic injections of SB-277011-A were found to (1) block enhancement of electrical brain stimulation reward by cocaine, (2) dose-dependently attenuate cocaine-induced conditioned place preference, and (3) dose-dependently attenuate cocaine-triggered reinstatement of cocaine seeking behavior. Thus, D₃ receptor blockade attenuates both the rewarding effects of cocaine and cocaine-induced drug-seeking behavior. These data suggest an important role for D₃ receptors in mediating the addictive properties of cocaine and suggest that blockade of dopamine D₃ receptors may constitute a new and useful target for prospective pharmacotherapies for cocaine addiction.

Key words: cocaine; addiction; dopamine; mesolimbic; mesocorticolimbic; D₃ receptor; D₃ antagonist; brain stimulation reward; BSR; self-stimulation; ICSS; conditioned place preference; CPP; self-administration; reinstatement; relapse

---

Copyright © 2002 Society for Neuroscience  0270-6474/02/22219595-09$05.00/0

This article has been cited by other articles:

				J. L. Martelle, R. Claytor, J. T. Ross, B. A. Reboussin, A. H. Newman, and M. A. Nader Effects of Two Novel D3-Selective Compounds, NGB 2904 [N-(4-(4-(2,3-Dichlorophenyl)piperazin-1-yl)butyl)-9H-fluorene-2-carboxamide] and CJB 090 [N-(4-(4-(2,3-Dichlorophenyl)piperazin-1-yl)butyl)-4-(pyridin-2-yl)benzamide], on the Reinforcing and Discriminative Stimulus Effects of Cocaine in Rhesus Monkeys J. Pharmacol. Exp. Ther., May 1, 2007; 321(2): 573 - 582. [Abstract] [Full Text] [PDF]

				I. Gyertyan, B. Kiss, K. Gal, I. Laszlovszky, A. Horvath, L. I. Gemesi, K. Saghy, G. Pasztor, M. Zajer, M. Kapas, et al. Effects of RGH-237 [N-{4-[4-(3-Aminocarbonyl-phenyl)-piperazin-1-yl]-butyl}-4-bromo-benzamide], an Orally Active, Selective Dopamine D3 Receptor Partial Agonist in Animal Models of Cocaine Abuse J. Pharmacol. Exp. Ther., March 1, 2007; 320(3): 1268 - 1278. [Abstract] [Full Text] [PDF]

				X. Luo, H. R. Kranzler, L. Zuo, S. Wang, N. J. Schork, and J. Gelernter Multiple ADH genes modulate risk for drug dependence in both African- and European-Americans Hum. Mol. Genet., February 15, 2007; 16(4): 380 - 390. [Abstract] [Full Text] [PDF]

				V. Vengeliene, F. Leonardi-Essmann, S. Perreau-Lenz, P. Gebicke-Haerter, K. Drescher, G. Gross, and R. Spanagel The dopamine D3 receptor plays an essential role in alcohol-seeking and relapse FASEB J, November 1, 2006; 20(13): 2223 - 2233. [Abstract] [Full Text] [PDF]

				H. Hammad and J. J. Wagner Dopamine-Mediated Disinhibition in the CA1 Region of Rat Hippocampus via D3 Receptor Activation J. Pharmacol. Exp. Ther., January 1, 2006; 316(1): 113 - 120. [Abstract] [Full Text] [PDF]

				F. J. Vocci, J. Acri, and A. Elkashef Medication Development for Addictive Disorders: The State of the Science Am J Psychiatry, August 1, 2005; 162(8): 1432 - 1440. [Abstract] [Full Text] [PDF]

				G. T. Collins, J. M. Witkin, A. H. Newman, K. A. Svensson, P. Grundt, J. Cao, and J. H. Woods Dopamine Agonist-Induced Yawning in Rats: A Dopamine D3 Receptor-Mediated Behavior J. Pharmacol. Exp. Ther., July 1, 2005; 314(1): 310 - 319. [Abstract] [Full Text] [PDF]

				B. Le Foll and S. R. Goldberg Cannabinoid CB1 Receptor Antagonists as Promising New Medications for Drug Dependence J. Pharmacol. Exp. Ther., March 1, 2005; 312(3): 875 - 883. [Abstract] [Full Text] [PDF]

				F. A. Champagne, P. Chretien, C. W. Stevenson, T. Y. Zhang, A. Gratton, and M. J. Meaney Variations in Nucleus Accumbens Dopamine Associated with Individual Differences in Maternal Behavior in the Rat J. Neurosci., April 28, 2004; 24(17): 4113 - 4123. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help