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Role of Dopamine in Addiction and Drug Abuse

February 22, 2012

Question:

“Please elaborate further on the role of dopamine in addiction and drug abuse.”

Jon W. Draud, MS, MD: 

This is a great question and I will approach it by discussing dopamine from a neuroimaging perspective.

Drugs of abuse are known to trigger large surges of dopamine extracellularly in limbic areas, specifically, nucleus accumbens. 1  Volkow et al 2-3  have shown that human imaging studies correlate descriptors of reward, ie, the “high” and euphoria with drug-induced increases in dopamine nucleus accumbens. There is also the issue of saliency of the reward, which seems to be driven by the novelty or unexpectedness of the activity. 4

Imaging studies have helped to uncover much of the complex story of dopamine in the addiction process, including measurement of neurochemical and metabolic processes; dopamine changes with drugs of abuse; and the issue of plastic changes with brain dopamine and how these lead to functional problems in patients with addictions.

Positron emission tomography (PET) studies have shown that intravenous administration of stimulants leads to fast dopamine changes and that oral dosing leads to slower dopamine surges. Volkow et al3, 5 have noted that the speed at which a substance enters the brain is correlated with the degree to which it may become reinforcing. For example, Brody et al6 have noted that there are very rapid surges induced after smoking tobacco or other substances.

This has led to the understanding that drugs of abuse manage to mimic, but greatly exceed the normal physiologic phasic firing of dopamine; the “normal” pathways of dopamine trafficking become “hijacked.” There are synaptic increases of dopamine during intoxication of both participants with addiction and without addiction, 1  but only a minority of participants truly become addicted and engage in compulsive substance abuse. Volkow et al 3-4  proposed that in vulnerable individuals there are changes in the neuroadaptations of the dopamine system involving reward, motivation, saliency, memory, and conditioning circuitry. Furthermore, there is much evidence to show that exposure to opiates, nicotine, or stimulants produce persistent adaptive changes in the dendritic trees of brain regions where reward circuitry is located.

Martinez et al7 have shown that patients addicted to numerous substances (heroin, alcohol, cocaine, and methamphetamine) all have reductions of dopamine 2 receptor density in striatum (including nucleus accumbens), which persist months after detoxification. This, of course, clinically provides a glimpse into issues of relapse and vulnerability even after substances are not currently being abused by our patients.

There are also functional and metabolic issues implicated by this long-term dopamine imbalance triggered by drug abuse. Ersche et al 8  have shown using PET studies that in alcoholics, marijuana abusers, and cocaine abusers, there is decreased activity in orbitofrontal cortex, cingulate gyrus, and dorsolateral prefrontal cortex. This is linked with decreased dopamine and receptor density and striatum. Indeed, in alcoholics this has been linked to craving severity and greater induced cue-activation of anterior cingulate gyrus and medial prefrontal cortex.

Dopamine also plays a role in the brain regions involved in memory, habit formation, and conditioning, namely hippocampus, dorsal striatum, and amygdala. 9  Understanding why some patients are more vulnerable to becoming addicted is of great clinical relevance. Volkow et al 10  have shown that patients who experience substances as pleasurable have greatly lowered levels of dopamine receptors compared with those who experience displeasure. This high dopamine and receptor density could actually protect against addiction. The theory is that there is higher metabolism of dopamine in these patients in areas of orbitofrontal cortex and cingulate gyrus, and this may dampen frontal circuits involved in salience and inhibitory control of limbic areas.

Treatment implications from this deeper understanding of dopamine’s role in addiction include strategies that should decrease the reward value of a patient’s drug of choice; weaken motivational drive to use drugs and dampen conditioned patterns of behavior; and, finally, strengthen frontal inhibition and executive control. Interestingly, both pharmacologic and nonpharmacologic treatment options accomplish these exact goals.

—Jon W. Draud, MS, MD

References

1. Koob GF, Bloom FE . Cellular and molecular mechanisms of drug dependence.  Science . 1988;242(4879):715-723.
2. Volkow ND, Wang GJ, Fowler JS, et al . Relationship between psychostimulant-induced "high" and dopamine transporter occupancy.  Proc Natl Acad Sci U S A . 1996;93(19):10388-10392.
3. Volkow ND, Fowler JS, Wang GJ, Swanson JM, Telang F . Dopamine in drug abuse and addiction: results of imaging studies and treatment implications.  Arch Neurol . Nov 2007;64(11):1575-1579.
4. Volkow ND, Swanson JM . Variables that affect the clinical use and abuse of methylphenidate in the treatment of ADHD.  Am J Psychiatry . 2003;160(11):1909-1918.
5. Volkow ND, Ding YS, Fowler JS, et al . Is methylphenidate like cocaine? Studies on their pharmacokinetics and distribution in the human brain.  Arch Gen Psychiatry . 1995;52(6):456-463.
6. Brody AL, Olmstead RE, London ED, et al . Smoking-induced ventral striatum dopamine release.  Am J Psychiatry . 2004;161(7):1211-1218.
7. Martinez D, Kim JH, Krystal J, Abi-Dargham A . Imaging the neurochemistry of alcohol and substance abuse. Neuroimaging Clin N Am. 2007;17(4):539-555, x.
8. Ersche KD, Fletcher PC, Roiser JP, et al . Differences in orbitofrontal activation during decision-making between methadone-maintained opiate users, heroin users and healthy volunteers.  Psychopharmacology (Berl) . 2006;188(3):364-373.
9. Volkow ND, Fowler JS, Wang GJ, Goldstein RZ . Role of dopamine, the frontal cortex and memory circuits in drug addiction: insight from imaging studies.  Neurobiol Learn Mem . 2002;78(3):610-624.
10. Volkow ND, Fowler JS, Wang GJ . Role of dopamine in drug reinforcement and addiction in humans: results from imaging studies.  Behav Pharmacol . 2002;13(5-6):355-366.

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