Book contents
- Introduction to Addiction Psychiatry
- Introduction to Addiction Psychiatry
- Copyright page
- Contents
- Preface
- 1 Population Impact: Epidemiology
- 2 Specific Symptom Sets: Clinical Phenomenology
- 3 A Disorder of Anatomical Structure and Function: Neurobiology
- 4 Biological Risk Amplification: Disease Vulnerability
- 5 Diagnosis and Treatment: Disease Tracking, Reduction, and Remission
- Index
- References
3 - A Disorder of Anatomical Structure and Function: Neurobiology
Published online by Cambridge University Press: 03 April 2025
Book contents
- Introduction to Addiction Psychiatry
- Introduction to Addiction Psychiatry
- Copyright page
- Contents
- Preface
- 1 Population Impact: Epidemiology
- 2 Specific Symptom Sets: Clinical Phenomenology
- 3 A Disorder of Anatomical Structure and Function: Neurobiology
- 4 Biological Risk Amplification: Disease Vulnerability
- 5 Diagnosis and Treatment: Disease Tracking, Reduction, and Remission
- Index
- References
Summary
The front door to addiction pathophysiology is through the nucleus accumbens (NAC) (aka, ventral striatum) – the brain’s primary neural network for representing, storing, and modifying motivational information. NAC motivational codes are informed and altered by converging axonal inputs from prefrontal cortex (PFC), hippocampal formation (HCF), and amygdala (AMY) that import cognitive and emotional information carried by glutamate (GLU) neurotransmission. Relaying motivational codes from NAC into the caudate-putamen (CA-PU; aka, dorsal striatum) influences the prioritization, sequencing, automaticity, and execution of complex, goal-directed motor programs. Four classes of stimuli increase dopamine (DA) neurotransmitter release into the NAC – events that are (1) rewarding, (2) unexpected, (3) stressful/painful, and (4) addictive drugs. The three classes of natural salient events promote DA discharge into the NAC to optimize flow of motivational information while operating as a learning signal for the creation and modification of new motivational codes and motor program sequences. In addiction pathogenesis, repeated drug delivery exploits the DA learning signal, causing abnormal changes in neuronal DNA expression, phenotypes, and axodendritic connections within the NAC network. This change in connectivity alters motivational codes managed and stored by the NAC network, so that motivated behavior driving drug use is involuntarily prioritized over other healthy motivations.
Keywords
- Type
- Chapter
- Information
- Introduction to Addiction Psychiatry , pp. 79 - 116Publisher: Cambridge University PressPrint publication year: 2025
References
Bechara, A., Damasio, H., Damasio, H. R., and Lee, G. P.. 1999. Different contributions of the human amygdala and ventromedial prefrontal cortex to decision-making. J Neurosci, 19: 5473–81.Google ScholarPubMed
Bernstein, H. G., Dobrowolny, H., Bogerts, B., Keilhoff, G., and Steiner, J.. 2019. The hypothalamus and neuropsychiatric disorders: Psychiatry meets microscopy. Cell Tissue Res, 375: 243–58.CrossRefGoogle ScholarPubMed
Berridge, K. C., and Robinson, T. E.. 1998. What is the role of dopamine in reward: Hedonic impact, reward learning, or incentive salience? Brain Res Rev, 28: 309–69.CrossRefGoogle ScholarPubMed
Centonze, D., Picconi, B., Gubellini, P., Bernardi, G., and Calabresi, P.. 2001. Dopaminergic control of synaptic plasticity in the dorsal striatum. Eur J Neurosci, 13: 1071–77.Google ScholarPubMed
Chambers, R. A., Bickel, W. K., and Potenza, M. N.. 2007. A scale-free systems theory of motivation and addiction. Neurosci Biobehav Rev, 31: 1017–45.CrossRefGoogle ScholarPubMed
Chandola, T., Head, J., and Bartley, M.. 2004. Socio-demographic predictors of quitting smoking: How important are household factors? Addiction, 99: 770–77.Google ScholarPubMed
Charney, D. S., Buxbaum, J. D., Sklar, P., and Nestler, E. J. (eds.). 2013. Neurobiology of Mental Illness. New York: Oxford University Press.CrossRefGoogle Scholar
Cummings, J. L. 1993. Frontal–subcortical circuits and human behavior. Arch Neurol, 50: 873–80.CrossRefGoogle ScholarPubMed
Graybiel, A. M. 1995. Building action repertoires: Memory and learning functions of the basal ganglia. Curr Opin Neurobiol, 5: 733–41.CrossRefGoogle ScholarPubMed
Graybiel, A M. 1998. The basal ganglia and chunking of action repertoires. Neurobiol Learn Mem, 70: 119–36.CrossRefGoogle ScholarPubMed
Green, R., Clark, A., Hickey, W., Hutsler, J., and Gazzaniga, M.. 1999. Braincutting for psychiatrists: The time is ripe. J Neuropsychiatry Clin Neurosci, 11: 301–06.CrossRefGoogle ScholarPubMed
Groenewegen, H. J., Wright, C. I., and Uylings, H. B. M.. 1997. The anatomical relationships of the prefrontal cortex with limbic structures and the basal ganglia. J Psychopharmacol, 11: 99–106.CrossRefGoogle ScholarPubMed
Gruber, A. J., Calhoon, G. G., Shusterman, I., Schoenbaum, G., Roesch, M. R., and O’Donnell, P.. 2010. More is less: A disinhibited prefrontal cortex impairs cognitive flexibility. J Neurosci, 30: 17102–10.CrossRefGoogle Scholar
Haber, S. N., Fudge, J. L., and McFarland, N. R.. 2000. Striatonigrostriatal pathways in primates form an ascending spiral from the shell to the dorsolateral striatum. J Neurosci, 20: 2369–82.CrossRefGoogle ScholarPubMed
Hollerman, J. R., Tremblay, L., and Schultz, W.. 2000. Involvement of basal ganglia and orbitofrontal cortex in goal directed behavior. Progr Brian Res, 126: 193–215.CrossRefGoogle ScholarPubMed
Jankovic, J. 2008. Parkinson’s disease: Clinical features and diagnosis. J Neurol Neurosurg Psychiatry, 79: 368–76.CrossRefGoogle ScholarPubMed
Kalivas, P. W., and O’Brien, C.. 2008. Drug addiction as a pathology of staged neuroplasticity. Neuoropsychophramacology, 33: 166–80.Google ScholarPubMed
Kalivas, P. W., and Volkow, N. D.. 2005. The neural basis of addiction: A pathology of motivation and choice. Am J Psychiatry, 162: 1403–13.Google ScholarPubMed
Kelley, A. E., and Berridge, K. C.. 2002. The neuroscience of natural rewards: Relevance to addictive drugs. J Neurosci, 22: 3306–11.CrossRefGoogle ScholarPubMed
Li, Y., Acerbo, M. J., and Robinson, T. E.. 2004. The induction of behavioral sensitization is associated with cocaine-induced structural plasticity in the core (but not shell) of the nucleus accumbens. Eur J Neurosci, 20: 1647–54.CrossRefGoogle Scholar
Malleret, G., Alarcon, J. M., Martel, G., Takizawa, S., Vronskaya, S., Yin, D., Chen, I. Z., Kandel, E. R., and Shumyatsky, G. P.. 2010. Bidirectional regulation of hippocampal long-term synaptic plasticity and its influence on opposing forms of memory. J Neurosci, 30: 3813–25.CrossRefGoogle ScholarPubMed
Nestler, E. J., and Aghajanian, G. K.. 1997. Molecular and cellular basis of addiction. Science, 278: 58–63.Google ScholarPubMed
O’Donnell, P., Greene, J., Pabello, N., Lewis, B. L., and Grace, A. A.. 1999. Modulation of cell firing in the nucleus accumbens. Ann N Y Acad Sci, 877: 157–75.Google ScholarPubMed
Redish, A. D. 2004. Addiction as a computational process gone awry. Science, 306: 1944–47.CrossRefGoogle ScholarPubMed
Redish, A. D., Jensen, S., and Johnson, A.. 2008. A unified framework for addiction: Vulnerabilities in the decision process. Behav Brain Sci, 31: 415–87.Google ScholarPubMed
Robinson, T. E., and Kolb, B.. 1999. Alterations in the morphology of dendrites and dendritic spines in the nucleus accumbens and prefrontal cortex following repeated treatment with amphetamine or cocaine. Eur J Neurosci, 11: 1598–604.CrossRefGoogle ScholarPubMed
Salmon, D. P., and Butters, N.. 1995. Neurobiology of skill and habit learning. Curr Opin Neurobiol, 5: 184–90.Google ScholarPubMed
Schultz, W., Dayan, P., and Montague, P. R.. 1997. A neural substrate of prediction and reward. Science, 275: 1593–99.Google ScholarPubMed
Self, D. W., and Nestler, E. J.. 1998. Relapse to drug-seeking: Neural and molecular mechanisms. Drug Alcohol Depend, 51: 49–60.CrossRefGoogle ScholarPubMed
Self, D. W., Terwilliger, R. Z., Nestler, E. J., and Stein, L.. 1994. Inactivation of Gi and Go proteins in nucleus accumbens reduces both cocaine and heroin reinforcement. J Neurosci, 14: 6239–47.Google ScholarPubMed
Steiner, H., and Tseng, K.-Y.. 2017. Handbook of Basal Ganglia Structure and Function. Amsterdam: Elsevier/Academic Press.Google Scholar
Widnell, K. L., Self, D. W., Lane, S. B., Russel, D. S., Vaidya, V. A., Miserendino, M. J. D., Rubin, C. S., Duman, R. S., and Nestler, E. J.. 1996. Regulation of CREB expression: In vivo evidence for a functional role of morphine action in the nucleus accumbens. J Psychopharmacol Exp Ther, 276: 306–15.Google ScholarPubMed
Wise, R. A. 1998. Drug-activation of brain reward pathways. Drug Alcohol Depend, 51: 13–22.CrossRefGoogle ScholarPubMed
Wise, R. A., and Bozarth, M. A.. 1987. A psychomotor stimulant theory of addiction. Psychol Rev, 94: 469–92.CrossRefGoogle ScholarPubMed
Wolf, M. E. 2002. Addiction: Making the connection between behavioral changes and neuronal plasticity in specific pathways. Mol Interv, 2: 146–57.CrossRefGoogle ScholarPubMed
Wolf, Y. I., Karev, G., and Koonin, E. V.. 2002. Scale-free networks in biology: New insights into fundamentals of evolution? Bioessays, 24: 105–09.CrossRefGoogle ScholarPubMed