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

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, March 31, 2004, 24(13):3344-3354; doi:10.1523/JNEUROSCI.0060-04.2004

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 (71) Citing Articles via Google Scholar Google Scholar Articles by Zhang, L. Articles by Xu, M. Search for Related Content PubMed PubMed Citation Articles by Zhang, L. Articles by Xu, M.

 Previous Article  |  Next Article 

Behavioral/Systems/Cognitive
Cocaine-Induced Intracellular Signaling and Gene Expression Are Oppositely Regulated by the Dopamine D1 and D3 Receptors

Lu Zhang,¹ Danwen Lou,¹ Hongyuan Jiao,¹ Dongsheng Zhang,¹ Xinkang Wang,³ Ying Xia,² Jianhua Zhang,¹ and Ming Xu¹

Departments of ¹Cell Biology, Neurobiology, and Anatomy, and ²Environmental Health, University of Cincinnati Medical Center, Cincinnati, Ohio 45267, and ³Department of Discovery Biology, Bristol-Myers Squibb Company, Princeton, New Jersey 08543

Repeated exposure to cocaine can induce neuroadaptations in the brain. One mechanism by which persistent changes occur involves alterations in gene expression mediated by the dopamine receptors. Both the dopamine D1 and D3 receptors have been shown to mediate gene expression changes. Moreover, the D1 and D3 receptors are also coexpressed in the same neurons, particularly in the nucleus accumbens and also caudoputamen (CPu). Little is known however, whether these two receptors coordinately regulate gene expression after cocaine administration and the underlying mechanisms. We have used various gene mutant mice to address this issue. We show that extracellular signal-regulated kinase (ERK) activation and c-fos induction in the CPu in response to acute cocaine administration is mediated by the D1 receptor and inhibited by the D3 receptor. Moreover, ERK activation mediates acute cocaine-induced expression of Fos family genes, including c-fos, fosB and fra2. Interestingly, dynorphin, neogenin, and synaptotagmin VII, genes that possess cAMP-response element binding protein and AP-1 transcription complex-binding consensus sequences in their promoters, are also oppositely regulated by the D1 and D3 receptors after repeated exposure to cocaine. Furthermore, such regulation depends on proper ERK activation and c-fos function. These results suggest that the D1 and D3 receptors elicit opposite regulation of target gene expression by regulating ERK activation and c-fos induction after acute and chronic cocaine treatment.

Key words: cocaine; dopamine receptors; signal transduction; mitogen-activated protein kinases; c-Fos; gene expression

---

Received Jan 7, 2004; revised February 13, 2004; accepted February 18, 2004.

This article has been cited by other articles:

				J. Bertran-Gonzalez, C. Bosch, M. Maroteaux, M. Matamales, D. Herve, E. Valjent, and J.-A. Girault Opposing Patterns of Signaling Activation in Dopamine D1 and D2 Receptor-Expressing Striatal Neurons in Response to Cocaine and Haloperidol J. Neurosci., May 28, 2008; 28(22): 5671 - 5685. [Abstract] [Full Text] [PDF]

				C. Zeng, I. Armando, Y. Luo, G. M. Eisner, R. A. Felder, and P. A. Jose Dysregulation of dopamine-dependent mechanisms as a determinant of hypertension: studies in dopamine receptor knockout mice Am J Physiol Heart Circ Physiol, February 1, 2008; 294(2): H551 - H569. [Abstract] [Full Text] [PDF]

				S. B. Caine, M. Thomsen, K. I. Gabriel, J. S. Berkowitz, L. H. Gold, G. F. Koob, S. Tonegawa, J. Zhang, and M. Xu Lack of Self-Administration of Cocaine in Dopamine D1 Receptor Knock-Out Mice J. Neurosci., November 28, 2007; 27(48): 13140 - 13150. [Abstract] [Full Text] [PDF]

				A. C. Boudreau, J. M. Reimers, M. Milovanovic, and M. E. Wolf Cell Surface AMPA Receptors in the Rat Nucleus Accumbens Increase during Cocaine Withdrawal But Internalize after Cocaine Challenge in Association with Altered Activation of Mitogen-Activated Protein Kinases J. Neurosci., September 26, 2007; 27(39): 10621 - 10635. [Abstract] [Full Text] [PDF]

				J. Zhang, L. Zhang, H. Jiao, Q. Zhang, D. Zhang, D. Lou, J. L. Katz, and M. Xu c-Fos Facilitates the Acquisition and Extinction of Cocaine-Induced Persistent Changes J. Neurosci., December 20, 2006; 26(51): 13287 - 13296. [Abstract] [Full Text] [PDF]

				J.-M. Beaulieu, T. D. Sotnikova, R. R. Gainetdinov, and M. G. Caron Paradoxical Striatal Cellular Signaling Responses to Psychostimulants in Hyperactive Mice J. Biol. Chem., October 27, 2006; 281(43): 32072 - 32080. [Abstract] [Full Text] [PDF]

				E. Valjent, A.-G. Corbille, J. Bertran-Gonzalez, D. Herve, and J.-A. Girault Inhibition of ERK pathway or protein synthesis during reexposure to drugs of abuse erases previously learned place preference PNAS, February 21, 2006; 103(8): 2932 - 2937. [Abstract] [Full Text] [PDF]

				J. Jeanblanc, D.-Y. He, N. N. H. McGough, M. L. Logrip, K. Phamluong, P. H. Janak, and D. Ron The Dopamine D3 Receptor Is Part of a Homeostatic Pathway Regulating Ethanol Consumption J. Neurosci., February 1, 2006; 26(5): 1457 - 1464. [Abstract] [Full Text] [PDF]

				K. Brami-Cherrier, E. Valjent, D. Herve, J. Darragh, J.-C. Corvol, C. Pages, A. J. Simon, J.-A. Girault, and J. Caboche Parsing Molecular and Behavioral Effects of Cocaine in Mitogen- and Stress-Activated Protein Kinase-1-Deficient Mice J. Neurosci., December 7, 2005; 25(49): 11444 - 11454. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help