Substance addiction and dopamine

Substance Abuse and its Global Impact

Substance abuse has caused health difficulties for people all around the world for thousands of years. Previously, it was a problem in the locations where the substances were produced, but due to international unlawful commerce, the problem has now become global. The harm caused by drug consumption to the nation’s health and, as a result, to economies in the form of low productivity and absence from the workplace. Controlling chemical addictions, as well as other types of addictions, is critical for the population’s well-being. To obtain it, people must understand how addictions occur in their brains, what processes regulate them, and what can be done to prevent addiction.

Understanding Substance Use Disorder

First, it is important to understand what modern medicine means by substance addiction as views on the problem change with time and may depend on culture. In USA medical advisers using Diagnostic and Statistical Manual of Mental Disorders (DSM-5) for classification among other disorders addictions. By this manual definition, substance-use disorder refers to “recurrent use of alcohol or other drugs that causes clinically and functionally significant impairment, such as health problems, disability, and failure to meet major responsibilities at work, school, or home. Depending on the level of severity, this disorder is classified as mild, moderate, or severe”. By the same manual definition ”the most severe, chronic stage of substance-use disorder, in which there is a substantial loss of self-control, as indicated by compulsive drug taking despite the desire to stop taking the drug“ named addiction (Volkow, Koob, & McLellan, 2016).

Brain Mechanisms of Addiction

Scientific studies on the brain mechanisms of addiction let hypothesize but do not give any univocal answer about the nature of drug abuse. The mainstream theory of addiction tells that this disorder has its roots in neuroadaptations in brain circuits induced by drugs, in particular in areas responsible for behavior motivation. As Covey writes, this alteration affects first dopamine reward circuit, therefore progress through the process of addiction may bound with dopamine. In the beginning of disorder, reinforcement of drug consumption comes from the effect of substances on ”midbrain dopamine neurons originating in the ventral tegmental area (VTA) and projecting to the nucleus accumbens (NAc)“ (Covey, Roitman, & Garris, 2014). In the result of intensive drug consumption extracellular dopamine increases in the medial shell of the NAc and in less degree in the NAc core and dorsal striatum. The elevation of dopamine in the NAc shell fixes the motivation to drug abuse, especially stimulants. The other effect of intensive drug consumption is ”a long-term potentiation at glutamatergic synapses onto dopamine neurons“ (Covey, Roitman, & Garris, 2014). The other changes in the brain leading to increasing dependence on drug abuse are plasticity in synapses in striatal regions and the ventromedial- to dorsolateral-directed progression in the primary striatal region caused by reciprocal feedback between midbrain dopamine neurons and the striatum (Covey, Roitman, & Garris, 2014). Development and amplification of association between drug and cue, the growing control of dopamine neurons projecting to the dorsolateral striatum over behavior in the result of the continuation of drug intake are responsible for the shift from goal-oriented consumption of substances to compulsive one (Covey, Roitman, & Garris, 2014). However, as Covey et al. notice the dopamine system and striatal regions are not exclusively responsible for addiction, other neurotransmitter systems and brain regions are also involved in the process of its development (Covey, Roitman, & Garris, 2014).

The Role of Dopamine in Addiction

From the description above, it is clear that modern science finds the role of dopamine in addiction arising highly important. In general form, the theory of addiction makes the difference between addictive and non-addictive drugs by the fact of dopamine release in the first case. As well, it states that striatal dopamine release is responsible for the euphoric effect, the experience of pleasure (the rewarding action) of abused substances and in particular of stimulant drugs (Caprioli, Calu, & Shaham, 2014).

Key Experiments on Addiction and Dopamine

The process of theory development started in the 1970s with studies on rats conducted by Olds and Milner. Animals in the laboratory were ”willingly and repeatedly self-stimulating particular areas in the brain with electricity“. This way the positive reinforcement mechanism has been discovered as well as the potential role of dopamine in addiction (Nutt, Lingford-Hughes, Erritzoe, & Stokes, 2015).

Scientists in Sardinia, Italy have conducted next experiments on rats with the application of the technique of brain microdialysis. An application of new research methods allowed finding the effect of abusive drugs on the level of ”dopamine release in the nucleus accumbens, which is located in the ventral striatum“ (Nutt, Lingford-Hughes, Erritzoe, & Stokes, 2015).

In 1994 scientists got the opportunity to image the human brain and, in particular, its dopamine system on humans. As well, they got an instrument for the measurement of dopamine release in the human striatum with ”the combination of intravenous infusion of a central stimulant drug and SPECT or PET neurochemical imaging of dopamine D2/3 receptors“ (Nutt, Lingford-Hughes, Erritzoe, & Stokes, 2015).

In the result of next experiments with different substances on humans, scientists got the contradictory results. First, there is positive evidence of dopamine release induction in humans only for some substances, mainly stimulants. Some studies of ketamine, cannabis, alcohol do not confirm the expected effects. Nutt, Lingford-Hughes, Erritzoe, & Stokes (2015) in their article provides a collection of experiments results both confirming and denying the theory. Results of experiments with marijuana are provided in their article Volkow et al. (2014). Main signs the scientists account as proof of the theory are lower striatal dopamine receptor availability and blunted dopamine release in the case of drug dependence (Nutt, Lingford-Hughes, Erritzoe, & Stokes, 2015).

A More Comprehensive Theory of Addiction

At the same time, there are many questions and arguments against the theory. Around questions are ones about the real importance of dopamine release in rewarding effects in the situation of drug abuse and application of the theory to non-stimulants groups of drugs (Caprioli, Calu, & Shaham, 2014). Around arguments are conflicting between lower receptor availability independent people and the necessity of D2 and/or D3 receptors for drug high experience that should lead to less reward with time and no progress of addiction (Nutt, Lingford-Hughes, Erritzoe, & Stokes, 2015). That confrontation led to the evolution of addiction theories and the inclusion of mesolimbic and nigrostriatal dopamine transmission in research as well as dopamine transmission in ventral and/or dorsal striatum (Caprioli, Calu, & Shaham, 2014).

Taking into account all arguments above I think that the view on addiction as a disorder of the dopamine neurotransmitter system that comes from the theory is limited. It does not bring many practical outcomes such as treatments for addicted people. Control on drugs inducing dopamine release often is counterproductive. The theory bears problems of analytical method, where scientists over concentrate on particular regions and neurotransmitters and pay little attention to the more complex interaction in the brain. Therefore, the more relevant theory of addiction should include various functioning of regions and transmitters in all their complexity.

Reference

Caprioli, D., Calu, D., & Shaham, Y. (2014). Loss of phasic dopamine: a new addiction marker?. Nature neuroscience, 17(5), 644-646.

Covey, D. P., Roitman, M. F., & Garris, P. A. (2014). Illicit dopamine transients: reconciling actions of abused drugs. Trends in neurosciences, 37(4), 200-210.

García‐García, I., Horstmann, A., Jurado, M. A., Garolera, M., Chaudhry, S. J., Margulies, D. S., ... & Neumann, J. (2014). Reward processing in obesity, substance addiction and non‐substance addiction. Obesity reviews, 15(11), 853-869.

Nutt, D. J., Lingford-Hughes, A., Erritzoe, D., & Stokes, P. R. (2015). The dopamine theory of addiction: 40 years of highs and lows. Nature Reviews. Neuroscience, 16(5), 305.

Volkow, N. D., Koob, G. F., & McLellan, A. T. (2016). Neurobiologic advances from the brain disease model of addiction. New England Journal of Medicine, 374(4), 363-371.

Volkow, N. D., Wang, G. J., Telang, F., Fowler, J. S., Alexoff, D., Logan, J., ... & Tomasi, D. (2014). Decreased dopamine brain reactivity in marijuana abusers is associated with negative emotionality and addiction severity. Proceedings of the National Academy of Sciences, 111(30), E3149-E3156.