Skip to main content Accessibility help
×
Home
  • Print publication year: 2020
  • Online publication date: July 2020

10 - Neurobiology of Substance Addictions

from Part III - Levels of Analysis and Etiology

Summary

Earlier neurobiological models of substance addictions proposed that addiction is the product of an imbalance between two separate, but interacting, neural systems: (1) an impulsive and amygdala-striatum dependent system that promotes automatic and habitual behaviors, and (2) a “reflective” prefrontal cortex dependent system for decision-making, forecasting the future consequences of a behavior, and inhibitory control. These impulsive and reflective systems are analogous to Daniel Kahneman’s model of System I and System II thinking, or the Behavioral Activation System (BAS) and the Behavioral Inhibition System (BIS). Here, the reflective system controls the impulsive system through several distinct mechanisms that regulate impulses. However, this control is not absolute – hyperactivity within the impulsive system can override the reflective system. Most prior research has focused either on the impulsive system (especially the ventral striatum and its mesolimbic dopamine projections) as a mechanism promoting the motivation and drive to seek drugs, or on the reflective system (prefrontal cortex) as a mechanism for decision-making and impulse control. More recent evidence suggests that a largely overlooked structure, the insula, also plays a key role in maintaining addiction (craving). Hence, a triadic model of addiction incorporates these three systems that are associated with archetypal behaviors in addiction: craving, motivation to procure the drug, poor decision-making, lack of impulse control, and deficits in self-regulation.

Related content

Powered by UNSILO
Ainslie, G. (1975). Specious reward: a behavioral theory of impulsiveness and impulse control. Psychological Bulletin, 82(4), 463496. http://doi.org/10.1037/h0076860
Amlung, M., Vedelago, L., Acker, J., Balodis, I. & MacKillop, J. (2017). Steep delay discounting and addictive behavior: a meta-analysis of continuous associations. Addiction, 112(1), 5162. https://doi.org/10.1111/add.13535
Baca, C. T. & Grant, K. J. (2007). What heroin users tell us about overdose. Journal of Addictive Diseases, 26(4), 6368. http://doi.org/10.1300/J069v26n04_08
Bachman, J. G., Johnston, L. D. & O’Malley, P. M. (1990). Explaining the recent decline in cocaine use among young adults: further evidence that perceived risks and disapproval lead to reduced drug use. Journal of Health and Social Behavior, 31(2), 173. http://doi.org/10.2307/2137171
Baxter, M. G. & Murray, E. A. (2002). The amygdala and reward. Nature Reviews Neuroscience. https://doi.org/10.1038/nrn875
Bayer, H. M. & Glimcher, P. W. (2005). Midbrain dopamine neurons encode a quantitative reward prediction error signal. Neuron, 47(1), 129141. http://doi.org/10.1016/J.NEURON.2005.05.020
Bechara, A. (2004). The role of emotion in decision-making: evidence from neurological patients with orbitofrontal damage. Brain and Cognition, 55(1), 3040.
Bechara, A. (2005). Decision making, impulse control and loss of willpower to resist drugs: a neurocognitive perspective. Nature Neuroscience, 8(11), 14581463. http://doi.org/10.1038/nn1584
Bechara, A. & Naqvi, N. (2004). Listening to your heart: interoceptive awareness as a gateway to feeling. Nature Neuroscience, 7(2), 102103. http://doi.org/10.1038/nn0204-102
Bechara, A., Damasio, H., Tranel, D. & Damasio, A. R., et al. (1997). Deciding advantageously before knowing the advantageous strategy. Science, 275(5304), 12931295. http://doi.org/10.1126/science.275.5304.1293
Bechara, A., Dolan, S., Denburg, N., et al. (2001). Decision-making deficits, linked to a dysfunctional ventromedial prefrontal cortex, revealed in alcohol and stimulant abusers. Neuropsychologia, 39(4), 376389. http://doi.org/10.1016/S0028-3932(00)00136-6
Belin, D., Jonkman, S., Dickinson, A., Robbins, T. W. & Everitt, B. J. (2009). Parallel and interactive learning processes within the basal ganglia: relevance for the understanding of addiction. Behavioural Brain Research, 199(1), 89102. http://doi.org/10.1016/J.BBR.2008.09.027
Berridge, K. C., Robinson, T. E. & Aldridge, J. W. (2009). Dissecting components of reward: “liking,” “wanting,” and learning. Current Opinion in Pharmacology, 9(1), 6573. http://doi.org/10.1016/J.COPH.2008.12.014
Bingel, U., Wanigasekera, V., Wiech, K., et al. (2011). The effect of treatment expectation on drug efficacy: imaging the analgesic benefit of the opioid remifentanil. Science Translational Medicine, 3(70), 70ra14. http://doi.org/10.1126/scitranslmed.3001244
Bjork, J. M. & Grant, S. J. (2009). Does traumatic brain injury increase risk for substance abuse? Journal of Neurotrauma, 26(7), 10771082. http://doi.org/http://dx.doi.org/10.1089/neu.2008.0849
Bowden-Jones, H., McPhillips, M., Rogers, R., Hutton, S. & Joyce, E. (2005). Risk-taking on tests sensitive to ventromedial prefrontal cortex dysfunction predicts early relapse in alcohol dependency: a pilot study. The Journal of Neuropsychiatry and Clinical Neurosciences, 17(3), 417420. https://doi.org/10.1176/jnp.17.3.417
Brody, A. L., Mandelkern, M. A., Olmstead, R. E., et al. (2009). Ventral striatal dopamine release in response to smoking a regular vs a denicotinized cigarette. Neuropsychopharmacology, 34(2), 282289. http://doi.org/10.1038/npp.2008.87
Carlson, R. W., Kumar, N. N., Wong-Mckinstry, E., et al. (2012). Alcohol withdrawal syndrome. Critical Care Clinics, 28(4), 549585. http://doi.org/10.1016/J.CCC.2012.07.004
Cicero, T. J., Ellis, M. S., Surratt, H. L. & Kurtz, S. P. (2014). The changing face of heroin use in the United States. JAMA Psychiatry, 71(7), 821. http://doi.org/10.1001/jamapsychiatry.2014.366
Clewett, D., Luo, S., Hsu, E., et al. (2014). Increased functional coupling between the left fronto-parietal network and anterior insula predicts steeper delay discounting in smokers. Human Brain Mapping. https://doi.org/10.1002/hbm.22436
Compton, W. M. & Volkow, N. D. (2006). Abuse of prescription drugs and the risk of addiction. Drug and Alcohol Dependence, 83, S4S7. http://doi.org/10.1016/j.drugalcdep.2005.10.020
Corrigall, W. A., Coen, K. M. & Adamson, K. L. (1994). Self-administered nicotine activates the mesolimbic dopamine system through the ventral tegmental area. Brain Research, 653(1–2), 278284. http://doi.org/10.1016/0006-8993(94)90401-4
Craig, A. D. (2009). How do you feel – now? The anterior insula and human awareness. Nature Reviews Neuroscience, 10(1), 5970. http://doi.org/10.1038/nrn2555
Craig, A. D. (2010). The sentient self. Brain Structure and Function, 214(5–6), 563577. http://doi.org/10.1007/s00429-010-0248-y
Crews, F., He, J. & Hodge, C. (2007). Adolescent cortical development: a critical period of vulnerability for addiction. Pharmacology Biochemistry and Behavior, 86(2), 189199. http://doi.org/10.1016/J.PBB.2006.12.001
Critchley, H. D., Wiens, S., Rotshtein, P., Öhman, A. & Dolan, R. J. (2004). Neural systems supporting interoceptive awareness. Nature Neuroscience, 7(2), 189195. http://doi.org/10.1038/nn1176
Dani, J. A. (2003). Roles of dopamine signaling in nicotine addiction. Molecular Psychiatry, 8(3), 255255. Retrieved from http://go.galegroup.com/ps/anonymous?id=GALE%7CA189963416&sid=googleScholar&v=2.1&it=r&linkaccess=fulltext&issn=13594184&p=AONE&sw=w&authCount=1&isAnonymousEntry=true
Daniulaityte, R., Falck, R. & Carlson, R. G. (2012). “I’m not afraid of those ones just ‘cause they’ve been prescribed”: perceptions of risk among illicit users of pharmaceutical opioids. International Journal of Drug Policy, 23(5), 374384. http://doi.org/10.1016/j.drugpo.2012.01.012
de la Fuente-Fernández, R., Phillips, A. G., Zamburlini, M., et al. (2002). Dopamine release in human ventral striatum and expectation of reward. Behavioural Brain Research, 136(2), 359363. http://doi.org/10.1016/S0166-4328(02)00130-4
Di Chiara, G., Bassareo, V., Fenu, S., et al. (2004). Dopamine and drug addiction: the nucleus accumbens shell connection. Neuropharmacology, 47, 227241. http://doi.org/10.1016/J.NEUROPHARM.2004.06.032
Droutman, V., Read, S. J. & Bechara, A. (2015). Revisiting the role of the insula in addiction. Trends in Cognitive Sciences, 19(7), 414420. http://doi.org/10.1016/J.TICS.2015.05.005
Everitt, B. J. & Robbins, T. W. (2005). Neural systems of reinforcement for drug addiction: from actions to habits to compulsion. Nature Neuroscience, 8(11), 14811489. http://doi.org/10.1038/nn1579
Everitt, B. J., Belin, D., Economidou, D., et al. W. (2008). Review: neural mechanisms underlying the vulnerability to develop compulsive drug-seeking habits and addiction. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, 363(1507), 31253135. http://doi.org/10.1098/rstb.2008.0089
Fein, G., Di Sclafani, V. & Meyerhoff, D. J. (2002). Prefrontal cortical volume reduction associated with frontal cortex function deficit in 6-week abstinent crack-cocaine dependent men. Drug and Alcohol Dependence, 68(1), 8793. http://doi.org/10.1016/S0376-8716(02)00110-2
Fleckenstein, A. E., Metzger, R. R., Wilkins, D. G., Gibb, J. W. & Hanson, G. R. (1997). Rapid and reversible effects of methamphetamine on dopamine transporters. Journal of Pharmacology and Experimental Therapeutics, 282(2), 834838. Retrieved from http://jpet.aspetjournals.org/content/282/2/834.abstract
Franklin, T. R., Acton, P. D., Maldjian, J. A., et al. (2002). Decreased gray matter concentration in the insular, orbitofrontal, cingulate, and temporal cortices of cocaine patients. Biological Psychiatry, 51(2), 134142. http://doi.org/10.1016/S0006-3223(01)01269-0
Fu, L. ping, Bi, G. Hua, Zou, Z. tong, et al. (2008). Impaired response inhibition function in abstinent heroin dependents: an fMRI study. Neuroscience Letters, 438(3), 322326. https://doi.org/10.1016/j.neulet.2008.04.033
Garavan, H. & Hester, R. (2007). The role of cognitive control in cocaine dependence. Neuropsychology Review. https://doi.org/10.1007/s11065-007-9034-x
Gardner, E. L. (2002). Addictive potential of cannabinoids: the underlying neurobiology. Chemistry and Physics of Lipids, 121, 267290. http://doi.org/10.1016/S0009-3084(02)00162-7
Gasquoine, P. G. (2014). Contributions of the insula to cognition and emotion. Neuropsychology Review, 24(2),7787. http://doi.org/10.1007/s11065-014-9246-9
Gessa, G., Melis, M., Muntoni, A. & Diana, M. (1998). Cannabinoids activate mesolimbic dopamine neurons by an action on cannabinoid CB1 receptors. European Journal of Pharmacology, 341(1), 3944. http://doi.org/10.1016/S0014-2999(97)01442-8
Gessa, G. L., Muntoni, F., Collu, M., Vargiu, L. & Mereu, G. (1985). Low doses of ethanol activate dopaminergic neurons in the ventral tegmental area. Brain Research, 348(1), 201203. http://doi.org/10.1016/0006-8993(85)90381-6
Goldman, D., Oroszi, G. & Ducci, F. (2005). The genetics of addictions: uncovering the genes. Nature Reviews Genetics, 6(7), 521532. http://doi.org/10.1038/nrg1635
Goldstein, R. Z. & Volkow, N. D. (2011). Dysfunction of the prefrontal cortex in addiction: neuroimaging findings and clinical implications. Nature Reviews Neuroscience. https://doi.org/10.1038/nrn3119
Gomes, T., Tadrous, M., Mamdani, M. M., Paterson, J. M. & Juurlink., D. N. (2018). The burden of opioid-related mortality in the United States. JAMA Network Open, 1(2), e180217. doi:10.1001/jamanetworkopen.2018.0217
Goudriaan, A. E., De Ruiter, M. B., Van Den Brink, W., Oosterlaan, J. & Veltman, D. J. (2010). Brain activation patterns associated with cue reactivity and craving in abstinent problem gamblers, heavy smokers and healthy controls: an fMRI study. Addiction Biology, 15(4), 491503. https://doi.org/10.1111/j.1369-1600.2010.00242.x
Graham, D. P. & Cardon, A. L. (2008). An update on substance use and treatment following traumatic brain injury. Annals of the New York Academy of Sciences, 1141, 148162. http://doi.org/10.1196/annals.1441.029
Grant, S., Contoreggi, C. & London, E. D. (2000). Drug abusers show impaired performance in a laboratory test of decision making. Neuropsychologia. https://doi.org/10.1016/S0028-3932(99)00158-X
Grau, L. E., Dasgupta, N., Harvey, A. P., et al. (2007). Illicit use of opioids: is OxyContin® a “gateway drug”? American Journal on Addictions, 16(3), 166173. http://doi.org/10.1080/10550490701375293
Gray, M. A. & Critchley, H. D. (2007). Interoceptive basis to craving. Neuron, 54(2), 183186. http://doi.org/10.1016/j.neuron.2007.03.024
Harlow, K. C. (1990). Patterns of rates of mortality from narcotics and cocaine overdose in Texas, 1976–87. Public Health Reports (Washington, D.C. : 1974), 105(5), 455462. Retrieved from www.ncbi.nlm.nih.gov/pubmed/2120721
Hasin, D. S., Saha, T. D., Kerridge, B. T., et al. (2015). Prevalence of marijuana use disorders in the United States between 2001–2002 and 2012–2013. JAMA Psychiatry, 72(12), 1235. http://doi.org/10.1001/jamapsychiatry.2015.1858
Hassan, S. F., Wearne, T. A., Cornish, J. L. & Goodchild, A. K. (2016). Effects of acute and chronic systemic methamphetamine on respiratory, cardiovascular and metabolic function, and cardiorespiratory reflexes. The Journal of Physiology, 594(3), 763780. http://doi.org/10.1113/JP271257
Heinz, A., Siessmeier, T., Wrase, J., et al. Correlation between dopamine D2 receptors in the ventral striatum and central processing of alcohol cues and craving. American Journal of Psychiatry, 161(10), 1783–1789. http://doi.org/10.1176/ajp.161.10.1783
Herz, A. (1997). Endogenous opioid systems and alcohol addiction. Psychopharmacology, 129(2), 99111. http://doi.org/10.1007/s002130050169
Hester, R. & Garavan, H. (2004). Executive dysfunction in cocaine addiction: evidence for discordant frontal, cingulate, and cerebellar activity. Journal of Neuroscience, 24(49), 1101711022. https://doi.org/10.1523/JNEUROSCI.3321-04.2004
Hill, J. C. & Toffolon, G. (1990). Effect of alcohol on sensory and sensorimotor visual functions. Journal of Studies on Alcohol, 51(2), 108113. http://doi.org/10.15288/jsa.1990.51.108
Hinson, J. M., Jameson, T. L. & Whitney, P. (2003). Impulsive decision making and working memory. Journal of Experimental Psychology: Learning, Memory, and Cognition, 29(2), 298306. http://doi.org/10.1037/0278-7393.29.2.298
Huang, Z.-L., Qu, W.-M., Eguchi, N., et al. (2005). Adenosine A2A, but not A1, receptors mediate the arousal effect of caffeine. Nature Neuroscience, 8(7), 858859. http://doi.org/10.1038/nn1491
Ito, R., Dalley, J. W., Robbins, T. W. & Everitt, B. J. (2002). Dopamine release in the dorsal striatum during cocaine-seeking behavior under the control of a drug-associated cue. The Journal of Neuroscience, 22(14), 6247 LP-6253. Retrieved from www.jneurosci.org/content/22/14/6247.abstract
Janes, A. C., Pizzagalli, D. A., Richardt, S., et al. (2010). Neural substrates of attentional bias for smoking-related Cues: an fMRI study. Neuropsychopharmacology. https://doi.org/10.1038/npp.2010.103
Jarmolowicz, D. P. & Schneider, T. D. (2020). Behavioral economics and addictive disorders. In Sussman, S. (Ed.) The Cambridge Handbook of Substance and Behavioral Addictions. Cambridge, UK: Cambridge University Press, pp. 1222.
Johnson, M. W., Bickel, W. K. & Kirshenbaum, A. P. (2004). Substitutes for tobacco smoking: A behavioral economic analysis of nicotine gum, denicotinized cigarettes, and nicotine-containing cigarettes. Drug and Alcohol Dependence, 74(3), 253264. http://doi.org/10.1016/j.drugalcdep.2003.12.012
Kaasinen, V., Aalto, S., Nagren, K. & Rinne, J. O. (2004). Expectation of caffeine induces dopaminergic responses in humans. European Journal of Neuroscience, 19(8), 23522356. http://doi.org/10.1111/j.1460-9568.2004.03310.x
Kaufman, J. N., Ross, T. J., Stein, E. A. & Garavan, H. (2003). Cingulate hypoactivity in cocaine users during a GO-NOGO task as revealed by event-related functional magnetic resonance imaging. Journal of Neuroscience, 23(21), 78397843. https://doi.org/10.1523/jneurosci.23-21-07839.2003
Khantzian, E. J. (1987). The self-medication hypothesis of addictive disorders: focus on heroin and cocaine dependence. In The Cocaine Crisis. Boston, MA: Springer US, pp. 6574. http://doi.org/10.1007/978-1-4613-1837-8_7
Kirby, K. N., Petry, N. M. & Bickel, W. K. (1999). Heroin addicts have higher discount rates for delayed rewards than non-drug-using controls. Journal of Experimental Psychology: General, 128(1), 7887. http://doi.org/10.1037/0096-3445.128.1.78
Koneru, A., Satyanarayana, S. & Rizwan, S. (2009). Endogenous opioids: their physiological role and receptors. Global Journal of Pharmacology, 3(3), 149153. Retrieved from https://pdfs.semanticscholar.org/e83a/851842f363f7e7f561c5ca465df9578d6bbc.pdf
Koob, G. F. & Volkow, N. D. (2010). Neurocircuitry of addiction. Neuropsychopharmacology, 35(1), 217238. http://doi.org/10.1038/npp.2009.110
Kringelbach, M. L. (2005). The human orbitofrontal cortex: linking reward to hedonic experience. Nature Reviews Neuroscience, 6(9), 691702. http://doi.org/10.1038/nrn1747
Krishnan-Sarin, S., Reynolds, B., Duhig, A. M., et al. (2007). Behavioral impulsivity predicts treatment outcome in a smoking cessation program for adolescent smokers. Drug and Alcohol Dependence, 88(1), 7982. https://doi.org/10.1016/j.drugalcdep.2006.09.006
Lin, S.-K., Pan, W. H. T. & Yeh, P.-H. (2007). Prefrontal dopamine efflux during exposure to drug-associated contextual cues in rats with prior repeated methamphetamine. Brain Research Bulletin, 71(4), 365371. http://doi.org/10.1016/J.BRAINRESBULL.2006.10.001
Marinkovic, K., Halgren, E. & Maltzman, I. (2004). Effects of alcohol on verbal processing: An event-related potential study. Alcoholism: Clinical & Experimental Research, 28(3), 415423. http://doi.org/10.1097/01.ALC.0000117828.88597.80
Mechtcheriakov, S., Brenneis, C., Egger, K., et al. (2007). A widespread distinct pattern of cerebral atrophy in patients with alcohol addiction revealed by voxel-based morphometry. Journal of Neurology, Neurosurgery, and Psychiatry, 78(6), 610614. http://doi.org/10.1136/jnnp.2006.095869
Melis, M., Pistis, M., Perra, S., et al. (2004). Endocannabinoids mediate presynaptic inhibition of glutamatergic transmission in rat ventral tegmental area dopamine neurons through activation of CB1 receptors. The Journal of Neuroscience:  The Official Journal of the Society for Neuroscience, 24(1), 5362. http://doi.org/10.1523/JNEUROSCI.4503-03.2004
Miech, R. A., Chilcoat, H. & Harder, V. S. (2005). The increase in the association of education and cocaine use over the 1980s and 1990s: Evidence for a “historical period” effect. Drug and Alcohol Dependence, 79(3), 311320. http://doi.org/10.1016/J.DRUGALCDEP.2005.01.022
Molina-Luna, K., Pekanovic, A., Röhrich, S., et al. (2009). Dopamine in motor cortex is necessary for skill learning and synaptic plasticity. PLoS ONE, 4(9), e7082. http://doi.org/10.1371/journal.pone.0007082
Monterosso, J. R., Ainslie, G., Xu, J., et al. (2007). Frontoparietal cortical activity of methamphetamine-dependent and comparison subjects performing a delay discounting task. Human Brain Mapping, 28(5), 383393. http://doi.org/10.1002/hbm.20281
Monterosso, J. R., Aron, A. R., Cordova, X., Xu, J. & London, E. D. (2005). Deficits in response inhibition associated with chronic methamphetamine abuse. Drug and Alcohol Dependence. https://doi.org/10.1016/j.drugalcdep.2005.02.002
Naqvi, N. H. & Bechara, A. (2005). The airway sensory impact of nicotine contributes to the conditioned reinforcing effects of individual puffs from cigarettes. Pharmacology Biochemistry and Behavior, 81(4), 821829. http://doi.org/10.1016/j.pbb.2005.06.005
Naqvi, N. H. & Bechara, A. (2009). The hidden island of addiction: the insula. Trends in Neurosciences, 32(1), 5667. http://doi.org/10.1016/j.tins.2008.09.009
Naqvi, N. H. & Bechara, A. (2010). The insula and drug addiction: an interoceptive view of pleasure, urges, and decision-making. Brain Structure and Function, 214(5–6), 435450. http://doi.org/10.1007/s00429-010-0268-7
Naqvi, N. H., Rudrauf, D., Damasio, H. & Bechara, A. (2007). Damage to the insula disrupts addiction to cigarette smoking. Science (New York, N.Y.), 315(5811), 531534. http://doi.org/10.1126/science.1135926
Nash, J. F. & Yamamoto, B. K. (1992). Methamphetamine neurotoxicity and striatal glutamate release: comparison to 3, 4-methylenedioxymethamphetamine. Brain Research, 581(2), 237243. http://doi.org/10.1016/0006-8993(92)90713-J
Nestler, E. J. (2005). The neurobiology of cocaine addiction. Science & Practice Perspectives, 3(1), 410. Retrieved from www.ncbi.nlm.nih.gov/pubmed/18552739
Noël, X., Brevers, D. & Bechara, A. (2013). A triadic neurocognitive approach to addiction for clinical interventions. Frontiers in Psychiatry, 4, 179. http://doi.org/10.3389/fpsyt.2013.00179
Oswald, L. M., Wong, D. F., McCaul, M., et al. (2005). Relationships among ventral striatal dopamine release, cortisol secretion and subjective responses to amphetamine. Neuropsychopharmacology, 30(4), 821832. http://doi.org/10.1038/sj.npp.1300667
Paraskevaides, T., Morgan, C. J. A., Leitz, J. R., et al. (2010). Drinking and future thinking: acute effects of alcohol on prospective memory and future simulation. Psychopharmacology, 208(2), 301308. http://doi.org/10.1007/s00213-009-1731-0
Pertwee, R. (2010). S.27.01 Pharmacological actions of cannabinoids. European Neuropsychopharmacology, 20, S205. http://doi.org/10.1016/S0924-977X(10)70232-7
Phillips, A. G. & Fibiger, H. C. (1979). Decreased resistance to extinction after haloperidol: implications for the role of dopamine in reinforcement. Pharmacology Biochemistry and Behavior, 10(5), 751760. http://doi.org/10.1016/0091-3057(79)90328-9
Pidoplichko, V. I., DeBiasi, M., Williams, J. T. & Dani, J. A. (1997). Nicotine activates and desensitizes midbrain dopamine neurons. Nature, 390(6658), 401404. http://doi.org/10.1038/37120
Pierce, R. C. & Kumaresan, V. (2006). The mesolimbic dopamine system: the final common pathway for the reinforcing effect of drugs of abuse? Neuroscience & Biobehavioral Reviews, 30(2), 215238. http://doi.org/10.1016/J.NEUBIOREV.2005.04.016
Porkka-Heiskanen, T., Strecker, R., Thakkar, M., Bjorkum, A. & Greene, R. (1997). Adenosine: a mediator of the sleep-inducing effects of prolonged wakefulness. Science, 276(5316), 12651268. http://doi.org/10.1126/science.276.5316.1265
Robbe, D., Kopf, M., Remaury, A., Bockaert, J. & Manzoni, O. J. (2002). Endogenous cannabinoids mediate long-term synaptic depression in the nucleus accumbens. Proceedings of the National Academy of Sciences of the United States of America, 99(12), 8384–8. http://doi.org/10.1073/pnas.122149199
Robbins, T. W., Ersche, K. D. & Everitt, B. J. (2008). Drug addiction and the memory systems of the brain. Annals of the New York Academy of Sciences, 1141(1), 121. http://doi.org/10.1196/annals.1441.020
Robinson, J. (2002). Decades of Drug Use: The ’80s and ’90s. Retrieved January 10, 2018, from http://news.gallup.com/poll/6352/decades-drug-use-80s-90s.aspx
Robinson, S., Sandstrom, S. M., Denenberg, V. H. & Palmiter, R. D. (2005). Distinguishing whether dopamine regulates liking, wanting, and/or learning about rewards. Behavioral Neuroscience, 119(1), 515. http://doi.org/10.1037/0735-7044.119.1.5
Robinson, T. E. & Berridge, K. C. (1993). The neural basis of drug craving: an incentive-sensitization theory of addiction. Brain Research Reviews, 18(3), 247291. http://doi.org/10.1016/0165-0173(93)90013-P
Robinson, T. E. & Berridge, K. C. (2001). Incentive-sensitization and addiction. Addiction, 96(1), 103114. http://doi.org/10.1046/j.1360-0443.2001.9611038.x
Roozendaal, B., McReynolds, J. R. & McGaugh, J. L. (2004). The basolateral amygdala interacts with the medial prefrontal cortex in regulating glucocorticoid effects on working memory impairment. The Journal of Neuroscience, 24(6), 1385 LP–1392. Retrieved from www.jneurosci.org/content/24/6/1385.abstract
Rossetti, Z. L., Hmaidan, Y. & Gessa, G. L. (1992). Marked inhibition of mesolimbic dopamine release: a common feature of ethanol, morphine, cocaine and amphetamine abstinence in rats. European Journal of Pharmacology, 221(2–3), 227234. http://doi.org/10.1016/0014-2999(92)90706-A
Rudd, R. A., Aleshire, N., Zibbell, J. E. & Matthew Gladden, R. (2016). Increases in drug and opioid overdose deaths – United States, 2000–2014. American Journal of Transplantation, 16(4), 13231327. http://doi.org/10.1111/ajt.13776
Samanez-Larkin, G. R., Hollon, N. G., Carstensen, L. L. & Knutson, B. (2008). Individual differences in insular sensitivity during loss: anticipation predict avoidance learning: research report. Psychological Science, 19(4), 320323. http://doi.org/10.1111/j.1467-9280.2008.02087.x
Schmidt, A., Borgwardt, S., Gerber, H., et al. (2014). Acute effects of heroin on negative emotional processing: relation of amygdala activity and stress-related responses. Biological Psychiatry, 76(4), 289296. http://doi.org/10.1016/j.biopsych.2013.10.019
Schoenbaum, G. & Shaham, Y. (2008). The role of orbitofrontal cortex in drug addiction: a review of preclinical studies. Biological Psychiatry, 63(3), 256262. http://doi.org/10.1016/J.BIOPSYCH.2007.06.003
Schoenbaum, G., Roesch, M. R. & Stalnaker, T. A. (2006). Orbitofrontal cortex, decision-making and drug addiction. Trends in Neurosciences, 29(2), 116124. http://doi.org/10.1016/j.tins.2005.12.006
Schultz, W. (1998). Predictive reward signal of dopamine neurons. Journal of Neurophysiology, 80(1), 127. http://doi.org/10.1152/jn.1998.80.1.1
Sell, L. A., Morris, J. S., Bearn, J., et al. (2000). Neural responses associated with cue evoked emotional states and heroin in opiate addicts. Drug and Alcohol Dependence, 60(2), 207216. http://doi.org/10.1016/S0376-8716(99)00158-1
Seymour, B., Daw, N., Dayan, P., Singer, T. & Dolan, R. (2007). Differential encoding of losses and gains in the human striatum. Journal of Neuroscience, 27(18), 48264831. http://doi.org/10.1523/JNEUROSCI.0400-07.2007
Shen, M., Piser, T. M., Seybold, V. S., et al. (1996). Cannabinoid receptor agonists inhibit glutamatergic synaptic transmission in rat hippocampal cultures. The Journal of Neuroscience : The Official Journal of the Society for Neuroscience, 16(14), 43224334. Retrieved from www.ncbi.nlm.nih.gov/pubmed/8699243
Singer, T., Critchley, H. D. & Preuschoff, K. (2009). A common role of insula in feelings, empathy and uncertainty. Trends in Cognitive Sciences, 13(8), 334340. http://doi.org/10.1016/j.tics.2009.05.001
Solinas, M., Ferré, S., You, Z.-B., et al. (2002). Caffeine induces dopamine and glutamate release in the shell of the nucleus accumbens. The Journal of Neuroscience, 22(15), 6321 LP–6324. Retrieved from www.jneurosci.org/content/22/15/6321.abstract
Spanagel, R., Herz, A. & Shippenberg, T. S. (1992). Opposing tonically active endogenous opioid systems modulate the mesolimbic dopaminergic pathway (mirodialysis/nucleus accumbens/dopamine release and metabolism/opiate dependence). Pharmacology, 89, 20462050. Retrieved from www.pnas.org/content/89/6/2046.full.pdf
Spiller, M. W., Broz, D., Wejnert, C., Nerlander, L., Paz-Bailey, G., Centers for Disease Control and Prevention (CDC), & National HIV Behavioral Surveillance System Study Group. (2015). HIV infection and HIV-associated behaviors among persons who inject drugs – 20 cities, United States, 2012. Morbidity and Mortality Weekly Report, 64(10), 270275. Retrieved from www.ncbi.nlm.nih.gov/pubmed/25789742
Stacy, A. W. & Wiers, R. W. (2010). Implicit cognition and addiction: a tool for explaining paradoxical behavior. Annual Review of Clinical Psychology, 6(1), 551575. http://doi.org/10.1146/annurev.clinpsy.121208.131444
Stacy, A. W., Pike, J. & Lee, A. Y. (2020). Multiple memory systems, addiction, and health habits: new routes for translational science. In Sussman, S. (Ed.) The Cambridge Handbook of Substance and Behavioral Addictions. Cambridge, UK: Cambridge University Press, pp. 152170.
Tanda, G., Pontieri, F. E. & Di Chiara, G. (1997). Cannabinoid and heroin activation of mesolimbic dopamine transmission by a common mu1 opioid receptor mechanism. Science (New York, N.Y.), 276(5321), 2048–50. http://doi.org/10.1126/SCIENCE.276.5321.2048
The Heroin Hug | Absolute Advocacy. (n.d.). Retrieved January 10, 2020, from www.absoluteadvocacy.org/the-heroin-hug/
Thompson, P. M., Hayashi, K. M., Simon, S. L., et al. (2004). Structural abnormalities in the brains of human subjects who use methamphetamine. The Journal of Neuroscience, 24(26), 6028 LP-6036. Retrieved from www.jneurosci.org/content/24/26/6028.abstract
Turcotte, C., Blanchet, M.-R., Laviolette, M. & Flamand, N. (2016). Impact of cannabis, cannabinoids, and endocannabinoids in the lungs. Frontiers in Pharmacology, 7, 317. http://doi.org/10.3389/fphar.2016.00317
Turel, O. & Bechara, A. (2016). A triadic reflective-impulsive-interoceptive awareness model of general and impulsive information system use: behavioral tests of neuro-cognitive theory. Frontiers in Psychology, 7, 601. http://doi.org/10.3389/fpsyg.2016.00601
Vaccarro, A. G. & Potenza, M. N. (2020). Neurobiological foundations of behavioral addictions. In Sussman, S. (Ed.) The Cambridge Handbook of Substance and Behavioral Addictions. Cambridge, UK: Cambridge University Press, pp. 136151.
Villafuerte, S., Heitzeg, M. M., Foley, S., et al. (2012). Impulsiveness and insula activation during reward anticipation are associated with genetic variants in GABRA2 in a family sample enriched for alcoholism. Molecular Psychiatry, 17(5), 511519. http://doi.org/10.1038/mp.2011.33
Volkow, N. D. & Fowler, J. S. (2000). Addiction, a disease of compulsion and drive: involvement of the orbitofrontal cortex. Cerebral Cortex, 10(3), 318325. http://doi.org/10.1093/cercor/10.3.318
Volkow, N. D., Chang, L., Wang, G.-J., et al. (2001). Loss of dopamine transporters in methamphetamine abusers recovers with protracted abstinence. The Journal of Neuroscience, 21(23), 94149418. Retrieved from www.jneurosci.org/content/21/23/9414.abstract
Volkow, N. D., Fowler, J. S., Wang, G.-J. & Swanson, J. M. (2004). Dopamine in drug abuse and addiction: results from imaging studies and treatment implications. Molecular Psychiatry, 9(6), 557569. http://doi.org/10.1038/sj.mp.4001507
Volkow, N. D., Wang, G.-J., Fowler, J. S., et al. (1996). Decreases in dopamine receptors but not in dopamine transporters in alcoholics. Alcoholism: Clinical and Experimental Research, 20(9), 15941598. http://doi.org/10.1111/j.1530-0277.1996.tb05936.x
Volkow, N. D., Wang, G.-J., Telang, F., et al. (2008). Dopamine increases in striatum do not elicit craving in cocaine abusers unless they are coupled with cocaine cues. NeuroImage, 39(3), 12661273. http://doi.org/10.1016/J.NEUROIMAGE.2007.09.059
Wager, T. D., Davidson, M. L., Hughes, B. L., Lindquist, M. A. & Ochsner, K. N. (2008). Prefrontal-subcortical pathways mediating successful emotion regulation. Neuron, 59(6), 10371050. http://doi.org/10.1016/J.NEURON.2008.09.006
Wang, Y., Zhu, L., Zou, Q., et al. (2018). Frequency dependent hub role of the dorsal and ventral right anterior insula. NeuroImage, 165, 112117. https://doi.org/10.1016/j.neuroimage.2017.10.004
Warlow, S. M., et al. (2020). Sensitization of incentive salience and the transition to addiction. In Sussman, S. (Ed.) The Cambridge Handbook of Substance and Behavioral Addictions. Cambridge, UK: Cambridge University Press, pp. 2337.
Watson, P., de Wit, S., Hommel, B. & Wiers, R. W. (2012). Motivational mechanisms and outcome expectancies underlying the approach bias toward addictive substances. Frontiers in Psychology, 3, 440. http://doi.org/10.3389/fpsyg.2012.00440
Westman, E. C., Behm, F. M. & Rose, J. E. (1995). Airway sensory replacement combined with nicotine replacement for smoking cessation: a randomized, placebo-controlled trial using a citric acid inhaler. Chest, 107(5), 13581364. http://doi.org/10.1378/CHEST.107.5.1358
Westman, E. C., Behm, F. M. & Rose, J. E. (1996). Dissociating the nicotine and airway sensory effects of smoking. Pharmacology Biochemistry and Behavior, 53(2), 309315. http://doi.org/10.1016/0091-3057(95)02027-6
What does it feel like to use cocaine? | Drug Policy Alliance. (n.d.). Retrieved January 9, 2020, from www.drugpolicy.org/drug-facts/cocaine/what-cocaine-feels-like
Wise, R. A. (1996). Neurobiology of addiction. Current Opinion in Neurobiology, 6(2), 243251. http://doi.org/10.1016/S0959-4388(96)80079-1
Yuan, Y., Zhu, Z., Shi, J., et al. (2009). Gray matter density negatively correlates with duration of heroin use in young lifetime heroin-dependent individuals. Brain and Cognition, 71(3), 223228. http://doi.org/10.1016/J.BANDC.2009.08.014