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Science 3 October 1997:
Vol. 278. no. 5335, pp. 58 - 63
DOI: 10.1126/science.278.5335.58
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Articles

Molecular and Cellular Basis of Addiction

Eric J. Nestler, * George K. Aghajanian

Drug addiction results from adaptations in specific brain neurons caused by repeated exposure to a drug of abuse. These adaptations combine to produce the complex behaviors that define an addicted state. Progress is being made in identifying such time-dependent, drug-induced adaptations and relating them to specific behavioral features of addiction. Current research needs to understand the types of adaptations that underlie the particularly long-lived aspects of addiction, such as drug craving and relapse, and to identify specific genes that contribute to individual differences in vulnerability to addiction. Understanding the molecular and cellular basis of addictive states will lead to major changes in how addiction is viewed and ultimately treated.

The authors are in the Laboratory of Molecular Psychiatry, Departments of Psychiatry and Pharmacology, Yale University School of Medicine and Connecticut Mental Health Center, 34 Park Street, New Haven, CT 06508, USA.
*   To whom correspondence should be addressed. E-mail: eric.nestler{at}qm.yale.edu

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Functional Interaction between Opioid and Cannabinoid Receptors in Drug Self-Administration.
M. Navarro, M. R. A. Carrera, W. Fratta, O. Valverde, G. Cossu, L. Fattore, J. A. Chowen, R. Gomez, I. del Arco, M. A. Villanua, et al. (2001)
J. Neurosci. 21, 5344-5350
   Abstract »    Full Text »    PDF »
Receptors and Transmission in the Brain-Gut Axis: Potential for Novel Therapies: III. {micro}-Opioid receptors in the enteric nervous system.
C. Sternini (2001)
Am J Physiol Gastrointest Liver Physiol 281, G8-G15
   Abstract »    Full Text »    PDF »
Heterologous Sensitization of Recombinant Adenylate Cyclases by Activation of D2 Dopamine Receptors.
M. G. Cumbay and V. J. Watts (2001)
J. Pharmacol. Exp. Ther. 297, 1201-1209
   Abstract »    Full Text »
The Role of Corticotropin-Releasing Factor in Drug Addiction.
Z. Sarnyai, Y. Shaham, and S. C. Heinrichs (2001)
Pharmacol. Rev. 53, 209-244
   Abstract »    Full Text »    PDF »
Modulations of Spinal Serotonin Activity Affect the Development of Morphine Tolerance.
J.-Y. Li, C.-H. Wong, E. Y.-K. Huang, Y.-C. Lin, Y.-L. Chen, P. P. C. Tan, and J.-C. Chen (2001)
Anesth. Analg. 92, 1563-1568
   Abstract »    Full Text »    PDF »
The Patient Recovering from Alcohol or Drug Addiction: Special Issues for the Anesthesiologist.
J. A. May, H. C. White, A. Leonard-White, D. C. Warltier, and P. S. Pagel (2001)
Anesth. Analg. 92, 1601-1608
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Expression Profiling of Neural Cells Reveals Specific Patterns of Ethanol-Responsive Gene Expression.
C. Thibault, C. Lai, N. Wilke, B. Duong, M. F. Olive, S. Rahman, H. Dong, C. W. Hodge, D. J. Lockhart, and M. F. Miles (2001)
Mol. Pharmacol. 58, 1593-1600
   Abstract »    Full Text »
Unifying Perspectives of the Mechanisms Underlying the Development of Tolerance and Physical Dependence to Opioids.
D. A. Taylor and W. W. Fleming (2001)
J. Pharmacol. Exp. Ther. 297, 11-18
   Abstract »    Full Text »
Limbic-Cortical-Ventral Striatal Activation during Retrieval of a Discrete Cocaine-Associated Stimulus: A Cellular Imaging Study with {gamma} Protein Kinase C Expression.
K. L. Thomas and B. J. Everitt (2001)
J. Neurosci. 21, 2526-2535
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Direct and Differential Interaction of {beta}-Arrestins with the Intracellular Domains of Different Opioid Receptors.
B. Cen, Y. Xiong, L. Ma, and G. Pei (2001)
Mol. Pharmacol. 59, 758-764
   Abstract »    Full Text »
Drug Addiction: To the Cortex...and Beyond!.
P. W. Kalivas (2001)
Am J Psychiatry 158, 349-350
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Effects of Chronic Ethanol Intake and Its Withdrawal on the Expression and Phosphorylation of the CREB Gene Transcription Factor in Rat Cortex.
S. C. Pandey, A. Roy, and N. Mittal (2001)
J. Pharmacol. Exp. Ther. 296, 857-868
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Altered gating of opiate receptor-modulated K+ channels on amygdala neurons of morphine-dependent rats.
X. Chen, H. G. Marrero, R. Murphy, Y.-J. Lin, and J. E. Freedman (2000)
PNAS 97, 14692-14696
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D2 Dopamine Receptors in Striatal Medium Spiny Neurons Reduce L-Type Ca2+ Currents and Excitability via a Novel PLC{beta}1-IP3-Calcineurin-Signaling Cascade.
S. Hernandez-Lopez, T. Tkatch, E. Perez-Garci, E. Galarraga, J. Bargas, H. Hamm, and D. J. Surmeier (2000)
J. Neurosci. 20, 8987-8995
   Abstract »    Full Text »    PDF »
Decreases in Endogenous Opioid Peptides in the Rat Medullo-Coerulear Pathway after Chronic Morphine Treatment.
E. J. Van Bockstaele, J. Peoples, A. S. Menko, K. McHugh, and G. Drolet (2000)
J. Neurosci. 20, 8659-8666
   Abstract »    Full Text »    PDF »


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