![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
EJ Nestler and JF Tallman
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06508.
We have studied a possible role for cyclic AMP-dependent protein kinase in mediating opiate addiction in the central nervous system by focusing on the rat locus coeruleus. This brain region is well suited for these studies because it is relatively homogeneous and because a wealth of electrophysiological and behavioral data indicate that it plays an important role in mediating the chronic effects of opiates in animals, including humans. It was found that chronic, but not acute, in vivo treatment of rats with morphine increased cyclic AMP-dependent protein kinase activity in the locus coeruleus with a time course that closely paralleled the time course by which locus coeruleus neurons become tolerant to and dependent on opiates, based on electrophysiological studies. Concomitant administration of the opiate receptor antagonist naltrexone was found to block the effect of chronic morphine treatment on protein kinase activity, indicating that the effect is mediated via specific activation of opiate receptors. In contrast, chronic morphine treatment did not alter protein kinase activity in several other brain regions studied, including the neostriatum, frontal cortex, and dorsal raphe. We propose that the observed increase in cyclic AMP-dependent protein kinase activity in the locus coeruleus contributes to the biochemical basis of opiate addiction.
This article has been cited by other articles:
|
|
 |
|
  A. R. Gintzler and S. Chakrabarti The Ambiguities of Opioid Tolerance Mechanisms: Barriers to Pain Therapeutics or New Pain Therapeutic Possibilities J. Pharmacol. Exp. Ther., June 1, 2008; 325(3): 709 - 713. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z.-Q. Wu, J. Chen, Z.-Q. Chi, and J.-G. Liu Involvement of Dopamine System in Regulation of Na+,K+-ATPase in the Striatum upon Activation of Opioid Receptors by Morphine Mol. Pharmacol., February 1, 2007; 71(2): 519 - 530. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Mouledous, J. Neasta, S. Uttenweiler-Joseph, A. Stella, M. Matondo, M. Corbani, B. Monsarrat, and J.-C. Meunier Long-Term Morphine Treatment Enhances Proteasome-Dependent Degradation of G{beta} in Human Neuroblastoma SH-SY5Y Cells: Correlation with Onset of Adenylate Cyclase Sensitization Mol. Pharmacol., August 1, 2005; 68(2): 467 - 476. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Chakrabarti, N.-J. Liu, and A. R. Gintzler Reciprocal modulation of phospholipase C{beta} isoforms: Adaptation to chronic morphine PNAS, November 11, 2003; 100(23): 13686 - 13691. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Wang, R. A. Barke, R. Charboneau, H. H. Loh, and S. Roy Morphine Negatively Regulates Interferon-{gamma} Promoter Activity in Activated Murine T Cells through Two Distinct Cyclic AMP-dependent Pathways J. Biol. Chem., September 26, 2003; 278(39): 37622 - 37631. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. McCahill, J. Warwicker, G. B. Bolger, M. D. Houslay, and S. J. Yarwood The RACK1 Scaffold Protein: A Dynamic Cog in Cell Response Mechanisms Mol. Pharmacol., December 1, 2002; 62(6): 1261 - 1273. [Full Text] [PDF]
|
|
|
|
 |
|
 T. Z. Shaw-Lutchman, M. Barrot, T. Wallace, L. Gilden, V. Zachariou, S. Impey, R. S. Duman, D. Storm, and E. J. Nestler Regional and Cellular Mapping of cAMP Response Element-Mediated Transcription during Naltrexone-Precipitated Morphine Withdrawal J. Neurosci., May 1, 2002; 22(9): 3663 - 3672. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Walters and J. A. Blendy Different Requirements for cAMP Response Element Binding Protein in Positive and Negative Reinforcing Properties of Drugs of Abuse J. Neurosci., December 1, 2001; 21(23): 9438 - 9444. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-Q. Kong, J. Meng, P. S. Biser, W. W. Fleming, and D. A. Taylor Cellular Depolarization of Neurons in the Locus Ceruleus Region of the Guinea Pig Associated with the Development of Tolerance to Opioids J. Pharmacol. Exp. Ther., September 1, 2001; 298(3): 909 - 916. [Abstract] [Full Text]
|
|
|
|
 |
|
 A. Ivanov and G. Aston-Jones Local Opiate Withdrawal in Locus Coeruleus Neurons In Vitro J Neurophysiol, June 1, 2001; 85(6): 2388 - 2397. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. L. Cichewicz, V. L. Haller, and S. P. Welch Changes in Opioid and Cannabinoid Receptor Protein following Short-Term Combination Treatment with {Delta}9-Tetrahydrocannabinol and Morphine J. Pharmacol. Exp. Ther., April 1, 2001; 297(1): 121 - 127. [Abstract] [Full Text]
|
|
|
|
|
|
S. L. Ingram, C. W. Vaughan, E. E. Bagley, M. Connor, and M. J. Christie Enhanced Opioid Efficacy in Opioid Dependence Is Caused by an Altered Signal Transduction Pathway J. Neurosci., December 15, 1998; 18(24): 10269 - 10276. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Numan, S. B. Lane-Ladd, L. Zhang, K. H. Lundgren, D. S. Russell, K. B. Seroogy, and E. J. Nestler Differential Regulation of Neurotrophin and trk Receptor mRNAs in Catecholaminergic Nuclei during Chronic Opiate Treatment and Withdrawal J. Neurosci., December 15, 1998; 18(24): 10700 - 10708. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. S. Rohde and A. I. Basbaum Activation of Coeruleospinal Noradrenergic Inhibitory Controls during Withdrawal from Morphine in the Rat J. Neurosci., June 1, 1998; 18(11): 4393 - 4402. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Noble and B. M. Cox The Role of Dopaminergic Systems in Opioid Receptor Desensitization in Nucleus Accumbens and Caudate Putamen of Rat After Chronic Morphine Treatment J. Pharmacol. Exp. Ther., November 1, 1997; 283(2): 557 - 565. [Abstract] [Full Text]
|
|
|
|
|
|
L. J. Punch, D. W. Self, E. J. Nestler, and J. R. Taylor Opposite Modulation of Opiate Withdrawal Behaviors on Microinfusion of a Protein Kinase A Inhibitor Versus Activator into the Locus Coeruleus or Periaqueductal Gray J. Neurosci., November 1, 1997; 17(21): 8520 - 8527. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Yabaluri and F. Medzihradsky Down-regulation of µ-Opioid Receptor by Full but Not Partial Agonists Is Independent of G Protein Coupling Mol. Pharmacol., November 1, 1997; 52(5): 896 - 902. [Abstract] [Full Text]
|
|
|
|
|
|
S. B. Lane-Ladd, J. Pineda, V. A. Boundy, T. Pfeuffer, J. Krupinski, G. K. Aghajanian, and E. J. Nestler CREB (cAMP Response Element-Binding Protein) in the Locus Coeruleus: Biochemical, Physiological, and Behavioral Evidence for a Role in Opiate Dependence J. Neurosci., October 15, 1997; 17(20): 7890 - 7901. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Meng, C. J. Malanga, J.-Q. Kong, D. A. Taylor, and W. W. Fleming Hyperpolarizing Effects of Morphine, Clonidine and 2-Chloroadenosine in Myenteric Neurons Associated with Tolerance to Morphine J. Pharmacol. Exp. Ther., April 1, 1997; 281(1): 41 - 47. [Abstract] [Full Text]
|
|
|
|
|
|
A. Bonci and J. T. Williams Increased Probability of GABA Release during Withdrawal from Morphine J. Neurosci., January 15, 1997; 17(2): 796 - 803. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Malanga, J. Meng, W. W. Fleming, and D. A. Taylor Chronic Morphine Treatment of Guinea Pigs Induces Nonspecific Sensitivity Changes in the Nucleus Tractus Solitarius In Vitro J. Pharmacol. Exp. Ther., January 1, 1997; 280(1): 16 - 23. [Abstract] [Full Text]
|
|
 |
 |
 |
|
 |
 |
 |
