34 AANA NewsBulletin ❙ January 2012 ❙ www.aana.com

PEER ASSISTANCE NEWS

How do Addicted Brains Differ from Nonaddicted Brains?E. Laura Wright, CRNA, PhD, MNA,

It gives me a great deal of pleasure to introduce this critical review of the neuroimaging science of addictive disorders written by E. Laura Wright, CRNA, PhD, MNA. Wright has recently joined the Health and Wellness Committee’s Peer Assistance Advisors Committee. Her doctoral research focused on those resilience factors that were part of the shared experience of CRNAs in long-term recovery from chemical dependency.

The evolving neuroscience that is beginning to define the persistent mor-phological and physiological alterations that are mediated by the processes involved in neuroplasticity are essential to our understanding of how the alterations in brain functioning parallel the alterations in physiology of other chronic diseases such as coronary artery disease. These diffuse altera-tions in brain physiology and downstream motivation, learning, and behav-iors underpin the chronic, progressive nature of addictive disorders.

I thank Dr. Wright for her significant contributions to our under-standing of the neuroscience, particularly as it applies to our recovering colleagues.

Art Zwerling, CRNA, DNP, DAAPM

Chair, Peer Assistance Advisors Committee

It is rare that someone has never been affected on some level by addiction. Often, it is easy to see the outward signs of chemical dependency as addicted coworkers or loved ones appear to make

incomprehensible choices, especially when they relapse. Under-standing some of the neurobiological underpinnings of the disease of addiction helps raise awareness about the challenges faced by those in recovery and can help explain why recovery is so difficult. Imaging studies of the brain provide a unique perspective of its neural activ-ity and illustrate some of the alterations noted in people with chemi-cal dependency.

Modern imaging techniques reveal that the brains of addicts are different. While there are several areas of the brain involved in the process of chemical dependency, certain areas involving dopaminergic neurons in the areas responsible for reward, memory, and inhibitory control, play significant roles in the desire, as well as the motivation, for acquiring the substance of abuse.1 This motivational reinforcement manifests as a craving and stimulates that overwhelming compulsion to seek and use. In fact, it is thought that the craving of an addic-tive substance is more an attribute of desire than it is the actual feel-ing of pleasure.2 In other words, the anticipation of pleasure is greater than the actual sensation of pleasure, and it is craving that motivates drug-seeking behavior. The brain learns to get pleasure from preced-ing events or cues that stimulate the desire. The pleasure associated

with anticipation becomes over-inflated and in a sense, the reward system is “hijacked.” The normal pleasure pathways are wired differ-ently. As chemical disease progresses, this sense of anticipation plays a larger role, feeding the addiction by inflating the reward and plea-sure associated with anticipation of the substance. The anticipation of the substance through associated activities becomes almost as reward-ing as the getting substance itself. This inflated reward associated with anticipation plays a large role in relapse. While in recovery, inadver-tent exposure to these substance-associated preceding activities stimu-lates a sudden craving, and if impulse control is not present or strong, these experiences can be overwhelming. A nurse anesthetist in recov-ery from fentanyl might experience this craving while in recovery when he or she holds a fentanyl vial or walks into an operating suite restroom. If mechanisms are not in place to deal with these intense anticipatory feelings, the sensations can greatly challenge the impulse control of that nurse anesthetist.

The nucleus accumbens is an area of the brain associated with a sense of pleasure. The ventral tegmental area is a mid-brain struc-ture that has dopamine projections into the nucleus accumbens. Stim-ulation of the ventral tegmental area with subsequent stimulation of the nucleus accumbens appears to play a large role in substance abuse and dependency as essentially all substances of abuse directly or indi-rectly stimulate one of them.3,4 While normal responses of pleasure to natural rewards such as food and sex result from dopamine release, drugs produce a more intense, but shorter acting dopamine response. Another important area for reinforcement of addictive behavior is the orbitofrontal cortex, which has projections to the ventral tegmental area.5

Neural activity can be detected with tracers attached to synthetic radioactive receptor agonists (positive emission tomography [PET]) scanning or tracers of glucose metabolism through functional magnetic resonance imaging (fMRI). Both techniques display a visual image of neural activity in response to particular stimuli. These types of imaging techniques reveal some very interesting differences between the chemi-cally dependent and non-chemically-dependent brains.

In the area of addiction, dopamine activity has been widely stud-ied. When cocaine addicts look at drug-related videos, they are likely to experience a craving.4 At the same time, PET scans reveal increased dopamine activity in certain areas of the brain that are not noted when non-drug-related videos are watched. Similar results have been seen with exposure to verbal cues.6 Mood altering drugs are not the only substances that result in altered brain activity. When high-calorie foods were shown to obese and non-obese women, greater dopamine activation was noted in particular areas of obese women’s brains, but not in those of the non-obese women.7

Another feature of addiction is a person’s loss of control of sub-

35www.aana.com ❙ January 2012 ❙ AANA NewsBulletin

PEER ASSISTANCE NEWS

stance intake. In chemically dependent brains, blunted dopamine activity has been noted in the areas of the brain responsible for inhi-bition of behavior. When medications that stimulate dopamine release and mimic dopamine activity were given to detoxified alcoholics, a reduced dopamine activity was noted when compared to non- alcoholics.8 Impulsivity scores have been negatively associated with reduced activity in some of the inhibitory areas of the brains such as the ventral striatum among detoxified alcoholics.9

Even at rest, brains of addicted individuals are different. When heroin abusers and their matched controls were asked to remain quiet with eyes closed, there was more spontaneous activity between the areas of reward such as the nucleus accumbens, ventral tegmental area, and orbitofrontal cortex.10 These areas were primed for activity.

Imaging genetically different brains is an emerging field. Investiga-tors have researched genes that modulate dopamine in the reward sys-tem and have shown that dopamine

2 receptor polymorphism affects

reward system processing configuration.11,12 In some variants, fewer receptors are expressed. Dopamine binding to these receptors is reduced as well.12 In an addict, this reduced sensitivity could result in desire and motivation to increase dopamine levels via his or her sub-stance of abuse. Another area of genetic imaging research involves the catabolism and re-uptake of dopamine. Synaptic dopamine levels are maintained by catechol-O-methyltransferase, which catabolizes syn-aptic dopamine, and the dopamine transporter enzyme, which trans-ports synaptic dopamine back into the presynaptic vesicle. Specific variants of either of these genes cause reduced expression and activ-ity of these enzymes, ultimately resulting in increased synaptic dopa-mine and increased activity in the prefrontal cortex and ventral stri-atum.11 In certain areas of the brain these variants have shown, via imaging studies, to have an altered reward processing response. This knowledge provides a foundation for understanding how genetic pre-disposition plays a role in reward and risk-taking behaviors associated with addiction.

SummaryImaging studies clearly show differences between the addicted brain and the nonaddicted brain. Most of these differences are in the areas that deal with reward processing. This processing, not only behav-ior, is dysfunctional in addiction. Functional neuroimaging techniques provide a deeper understanding about the intricacies of how the brain functions and may play a future role in predicting those at risk, as well as evaluating treatment and recovery programs.■

References1. Koob GF, Le Moal M. Addiction and the brain antireward system.

Annu Rev Psychol. 2008;59:29-53.2. Koob GF, Volkow ND. Neurocircuitry of addiction. Neuropsycho-

pharmacology. 2010;35:217-238. 3. Nestler EJ. Is there a common molecular pathway for addiction?

Nat Neurosci. 2005;8:1445-1449.4. Volkow ND, Wang GJ, Telang F, et al. Cocaine cues and dopamine

in dorsal striatum: mechanism of craving in cocaine addiction. J Neurosci. 2006;26:6583-6588.

5. Volkow ND, Fowler JS, Wang GJ, Baler R, Telang F. Imaging dopa-mine’s role in drug abuse and addiction. Neuropharmacology. 2009;56 Suppl 1:3-8.

6. Goldstein RZ, Tomasi D, Alia-Klein N, et al. Dopaminer-gic response to drug words in cocaine addiction. J Neurosci. 2009;29:6001-6006.

7. Stoeckel LE, Weller RE, Cook EW 3rd, Twieg DB, Knowl-ton RC, Cox JE. Widespread reward-system activation in obese women in response to pictures of high-calorie foods. Neuroimage. 2008;41:636-647.

8. Volkow ND, Wang GJ, Telang F, et al. Profound decreases in dopa-mine release in striatum in detoxified alcoholics: possible orbito-frontal involvement. J Neurosci. 2007 Nov 14;27:12700-1276.

9. Dom G, Sabbe B, HylstijnW, van den Brink W. (2009). Substance use disorders and the orbitofrontal cortex systematic review of behavioural decision-making and neuroimaging studies. Br J Psy-chiatry. 2005;187:209-220.

10. Ma N, Liu Y, Li N, et al. Addiction related alteration in resting-state brain connectivity. Neuroimage. 2010;49:738-744.

11. Dreher JC, Kohn P, Kolachana B, Weinberger DR, Berman KF. Variation in dopamine genes influences responsivity of the human reward system. Proc Natl Acad Sci U S A. 2009;13:15106-15111.

12. Kirsch P, Reuter M, Mier D, et al. Imaging gene-substance interac-tions: the effect of the DRD2 TaqIA polymorphism and the dopa-mine agonist bromocriptine on the brain activation during the anticipation of reward. Neurosci Lett. 2006;405:196-201.

E. Laura Wright, CRNA, PhD, MNA, is assistant professor and interim program director, UAB Nurse Anesthesia Program, Birmingham, Ala.