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

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, June 8, 2005, 25(23):5553-5562; doi:10.1523/JNEUROSCI.0345-05.2005

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 (47) Citing Articles via Google Scholar Google Scholar Articles by Olson, V. G. Articles by Nestler, E. J. Search for Related Content PubMed PubMed Citation Articles by Olson, V. G. Articles by Nestler, E. J.

 Previous Article  |  Next Article 

Development/Plasticity/Repair
Regulation of Drug Reward by cAMP Response Element-Binding Protein: Evidence for Two Functionally Distinct Subregions of the Ventral Tegmental Area

Valerie G. Olson,¹ Cyrus P. Zabetian,^1,2 Carlos A. Bolanos,¹ Scott Edwards,¹ Michel Barrot,¹ Amelia J. Eisch,¹ Thomas Hughes,³ David W. Self,¹ Rachael L. Neve,⁴ and Eric J. Nestler¹

¹Department of Psychiatry and Center for Basic Neuroscience, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-9070, ²Department of Psychiatry, Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut 06516, ³Department of Ophthalmology, Yale University School of Medicine, New Haven, Connecticut 06510, and ⁴Department of Psychiatry, Harvard Medical School and McLean Hospital, Belmont, Massachusetts 02478

The transcription factor cAMP response element binding protein (CREB) is implicated in the actions of drugs of abuse in several brain areas, but little information is available about a role for CREB in the ventral tegmental area (VTA), one of the key reward regions of the brain. Here, we demonstrate that chronic exposure to drugs of abuse induces CREB activity throughout the VTA. Using viral-mediated gene transfer, we expressed green fluorescent protein (GFP)-tagged CREB or mCREB (a dominant-negative form of CREB) in the VTA and, using a conditioned place-preference paradigm, found that CREB activation within the rostral versus caudal subregions of the VTA produces opposite effects on drug reward. We identified VTA subregion-specific differences in the proportion of dopaminergic and GABAergic neurons and in the dopaminergic projections to the nucleus accumbens, another brain region implicated in drug reward, and suggest that this may contribute to behavioral differences in this study. We also measured expression levels of tyrosine hydroxylase and the AMPA glutamate receptor subunit GluR1, both of which are known to contribute to drug reward in the VTA, and found that both of these genes are upregulated following the expression of CREB-GFP and downregulated following expression of mCREB-GFP, raising the possibility that CREB may exert its effects on drug reward, in part, via regulation of these genes. These results suggest a novel role for CREB in mediating drug-induced plasticity in the VTA and establish two functionally distinct subregions of the VTA in which CREB differentially regulates drug reward.

Key words: cocaine; reward; ventral tegmental area; CREB; mesocortical; mesolimbic; morphine

---

Received April 1, 2004; revised April 15, 2005; accepted April 17, 2005.

This article has been cited by other articles:

				F. Brischoux, S. Chakraborty, D. I. Brierley, and M. A. Ungless Phasic excitation of dopamine neurons in ventral VTA by noxious stimuli PNAS, March 24, 2009; 106(12): 4894 - 4899. [Abstract] [Full Text] [PDF]

				B. van Zundert, M. H. Peuscher, M. Hynynen, A. Chen, R. L. Neve, R. H. Brown Jr, M. Constantine-Paton, and M. C. Bellingham Neonatal Neuronal Circuitry Shows Hyperexcitable Disturbance in a Mouse Model of the Adult-Onset Neurodegenerative Disease Amyotrophic Lateral Sclerosis J. Neurosci., October 22, 2008; 28(43): 10864 - 10874. [Abstract] [Full Text] [PDF]

				D. A. Lane, A. A. Lessard, J. Chan, E. E. O. Colago, Y. Zhou, S. D. Schlussman, M. J. Kreek, and V. M. Pickel Region-Specific Changes in the Subcellular Distribution of AMPA Receptor GluR1 Subunit in the Rat Ventral Tegmental Area after Acute or Chronic Morphine Administration J. Neurosci., September 24, 2008; 28(39): 9670 - 9681. [Abstract] [Full Text] [PDF]

				M. F. Kritzer and L. M. Creutz Region and Sex Differences in Constituent Dopamine Neurons and Immunoreactivity for Intracellular Estrogen and Androgen Receptors in Mesocortical Projections in Rats J. Neurosci., September 17, 2008; 28(38): 9525 - 9535. [Abstract] [Full Text] [PDF]

				M. Shabat-Simon, D. Levy, A. Amir, M. Rehavi, and A. Zangen Dissociation between Rewarding and Psychomotor Effects of Opiates: Differential Roles for Glutamate Receptors within Anterior and Posterior Portions of the Ventral Tegmental Area J. Neurosci., August 20, 2008; 28(34): 8406 - 8416. [Abstract] [Full Text] [PDF]

				J.-H. Han, A. P. Yiu, C. J. Cole, H.-L. Hsiang, R. L. Neve, and S. A. Josselyn Increasing CREB in the auditory thalamus enhances memory and generalization of auditory conditioned fear Learn. Mem., May 30, 2008; 15(6): 443 - 453. [Abstract] [Full Text] [PDF]

				Z. A. Rodd, V. E. Gryszowka, J. E. Toalston, S. M. Oster, D. Ji, R. L. Bell, and W. J. McBride The Reinforcing Actions of a Serotonin-3 Receptor Agonist within the Ventral Tegmental Area: Evidence for Subregional and Genetic Differences and Involvement of Dopamine Neurons J. Pharmacol. Exp. Ther., June 1, 2007; 321(3): 1003 - 1012. [Abstract] [Full Text] [PDF]

				Y.-S. Hsieh, S.-F. Yang, and D.-Y. Kuo Intracerebral administration of protein kinase A or cAMP response element-binding protein antisense oligonucleotide can modulate amphetamine-mediated appetite suppression in free-moving rats Am J Physiol Endocrinol Metab, January 1, 2007; 292(1): E123 - E131. [Abstract] [Full Text] [PDF]

				J. McDaid, M. P. Graham, and T. C. Napier Methamphetamine-Induced Sensitization Differentially Alters pCREB and {Delta}FosB throughout the Limbic Circuit of the Mammalian Brain Mol. Pharmacol., December 1, 2006; 70(6): 2064 - 2074. [Abstract] [Full Text] [PDF]

				S. Li, M. L. Lee, M. R. Bruchas, G. C. Chan, D. R. Storm, and C. Chavkin Calmodulin-Stimulated Adenylyl Cyclase Gene Deletion Affects Morphine Responses Mol. Pharmacol., November 1, 2006; 70(5): 1742 - 1749. [Abstract] [Full Text] [PDF]

				M.-H. Han, C. A. Bolanos, T. A. Green, V. G. Olson, R. L. Neve, R.-J. Liu, G. K. Aghajanian, and E. J. Nestler Role of cAMP response element-binding protein in the rat locus ceruleus: regulation of neuronal activity and opiate withdrawal behaviors. J. Neurosci., April 26, 2006; 26(17): 4624 - 4629. [Abstract] [Full Text] [PDF]

				S. Ikemoto, M. Qin, and Z.-H. Liu Primary Reinforcing Effects of Nicotine Are Triggered from Multiple Regions Both Inside and Outside the Ventral Tegmental Area J. Neurosci., January 18, 2006; 26(3): 723 - 730. [Abstract] [Full Text] [PDF]

				D. Ron and R. Jurd The "Ups and Downs" of Signaling Cascades in Addiction Sci. Signal., November 8, 2005; 2005(309): re14 - re14. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help