Motivation and emotion/Book/2017/Dopamine and drug addiction

Overview
The use and abuse of substances, whether it be illicit drugs, alcohol or nicotine, has serious implications for public health and is a major issue in today's society. In Australia alone, alcohol-related problems cost society over $14 billion in 2010 (Manning, Smith & Mazerolle, 2013) and the cost of illicit drug-use was estimated to be over $8 billion in 2004-05 (Collins & Lapsley, 2008). Substance abuse also impacts the health and wellbeing of those consumed by or struggling to break free of the addiction. It is critical to understand the underlying mechanisms that motivate drug addiction in order to develop strategies and treatments to combat substance abuse.

This book chapter discusses the role that dopamine plays in drug use and addiction, how it motivates behaviour, and how this knowledge can be used to combat addiction. The function of dopamine, relevant theories and mechanisms of motivation, and empirical evidence supporting the validity of these theories in explaining dopamine's influence on addiction is discussed, as well as treatments and strategies that have arisen from empirical research.

What is dopamine?


Dopamine is a naturally produced brain chemical that functions as a neurotransmitter. Neurotransmitters are used to transmit messages from one neuron to the next, and in turn result in the transmission of messages between different brain structures. Dopamine operates in the neural pathway that communicates messages between brain structures that are involved in reward and pleasure (Reeve, 2015). This means that dopamine is responsible feelings of reward and pleasure. Environmental and internal stimuli trigger the synthesis of dopamine within the ventral tegmental area (VTA), a subcortical structure. Neurons in VTA project into the nucleus accumbens (NA), which receive the message relayed by dopamine. The NA then produces the pleasure, while the VTA relays the pleasure message to the prefrontal cortex, which brings the pleasure to conscious awareness.

Reward 'centre'


In 1954, Olds and Milner discovered that rats who were given brief brain stimulation repeated behaviours preceding the stimulation and returned to the place it had occurred. Early theories like Freud (1915) and Hull's (1943) drive theory and Maslow's hierarchy of needs (1943), suggested that basic biological needs underly motivation and motivated behaviour. However, in this experiment, the behaviour was not motivated by basic biological needs like food, but rather by the desire for pleasure, as the brain stimulation had activated an area of the brain that Olds and Milner (1954) concluded was the pleasure (or reward) centre.

Olds and Fobes (1981) explain that the reward centre is not one "centre" or brain structure, but rather a complex system consisting of a number of subcortical structures. The VTA and NA constitute the basis of the dopamine-based reward centre (Reeve, 2015), and other structures that have been found to be involved include the dorsal striatum, hippocampus, hypothalamus, amygdala, and the parabrachial nucleus (Berridge & Kringelbach, 2015; Nestler, Hyman, & Malenka, 2009; Yager, Garcia, Wunsch, & Ferguson, 2015).

The Brain

There are so many different brain areas and structures that it can be hard to keep up. Follow this link to an interactive map of the brain, with descriptions of each brain area and their functions!

Dual-process model
The brain can be categorised into cortical and subcortical areas. Typically, the subcortical areas deal with basic, unconscious and automatic motivational processes, such as urges, impulses and desires. The cortical areas deal with complex motivational processes, such as conscious thought, planning and beliefs. Although these two areas deal with different motivational processes, they each play a part in both motivation and motivated behaviour. Information from both areas are shared and integrated through neural networks that transmit information from one neuron to the next, and eventually to other brain structures (Reeve, 2015). This information transmission is facilitated through neurotransmitters, such as serotonin, dopamine, norepinephrine and endorphins, which each use specific neural pathways and each transmit specific messages. For example, serotonin sends messages regarding mood and dopamine sends messages regarding reward and pleasure (Reeve, 2015). Gladwin, Figner, Crone and Wiers (2011) explained that subcortical regions exert a bottom-up influence on motivation, meaning that motivation is driven more by impulses generated by subcortical structures, whilst the cortical regions exert a top-down influence, meaning that motivation and behaviour is directed by conscious decision making.

The dual-process model suggests that motivation and motivated behaviour do not simply arise from the stimulation and activity of one independent brain area, but rather are the result of the integration and interconnectivity of many brain structures (O'Doherty, 2004). This model acknowledges the influence of subcortical structures that constitute the reward centre (Olds & Fobes, 1954) and the influence of cortical regions (including conscious awareness), as well as the influence of the integration of their information.

Law of Effect and Operant Conditioning


The previous mechanisms discussed explain that dopamine plays an active part in motivation and motivated behaviour via biological and physiological systems and processes and provides insight into the mechanisms that should be considered when seeking to alter motivation and behaviour. However, these explanations do not give as much insight into the process by which these motivations and behaviours become an ingrained, habitual or addictive.

Thorndike's Law of Effect (1911) paved the way for Behaviourism and revealed crucial mechanisms that influence motivation and behaviour. Thorndike's research involved placing cats in puzzle boxes, with the only means of escape being pulling a metal loop. Over a number of trials, ineffective behaviours like scratching the walls decreased as they did not result in escape, whereas the successful behaviour of pulling the loop dramatically increased. Thorndike (1911;1932) theorised that responses to situations that lead to successful outcomes become linked to the situation, so when one encounters the same or similar situation, the previously successful response is more likely to occur. This theory can be used to explain addictive behaviour, as the consumption of substances often results in a positive outcome (pleasure), which makes consumptive behaviour more likely in future situations.

The same premise that underlies the Law of Effect also underlies operant conditioning: the consequences of a response (pleasure or distress) influence the future occurrence of that response. Operant conditioning, most commonly associated with B. F. Skinner, has a more complex approach to learning, emphasising the influence of both positive and negative reward and punishment on increasing or decreasing the occurrence of behaviour.

These theories can be applied in the context of dopamine and motivation. From a biological perspective, reward or pleasure is simply the release of dopamine, which stimulates positive affect (D’Ardenne, McClure, Nystrom, & Cohen, 2008). The positive effects of a behaviour is the release of dopamine in the reward centre (Reeve, 2015).

Illicit drugs
The use of illicit drugs is a huge problem in Australia. Since the beginning of the 21st century, the death rate due to illicit drugs like methamphetamines such as "ice" have quadrupled (Australian Bureau of Statistics, 2017). Recent data has found that more than 3 million Australians regularly use, or have used at least once, illicit substances, ranging from cannabis to methamphetamines (Australian Institute of Health and Welfare, 2017).



Studies have demonstrated the role that dopamine plays in drug motivation. For example, one imaging study used PET scans to assess the influence of cocaine on dopamine levels and dopamine receptors in humans and found an increase in dopamine levels in brain areas related to the reward centre, like the striatum (Volkow, Fowler, Wang & Swanson, 2007). Another study measured the effect of cocaine on dopamine levels in mice and found that cocaine resulted in an increase in dopamine levels in the nucleus accumbens (NA), and that this increase was involved in mediating cocaine reward (Chen et al., 2006). This study demonstrates dopamine's influence on the brain's reward centre, which involves the nucleus accumbens.

Other studies have found that cortical structures like the orbitofrontal cortex and the anterior cingulate gyrus mediate the influence of dopamine on motivation (Schultz, 2002). These two areas are involved in assigning value to reinforcers (drugs) (Volkow, Fowler, Wang, Swanson & Telang, 2007). One imaging study found decreased activity in these areas in participants with cocaine or methamphetamine addictions, which also resulted in reduced activity of dopamine receptors in the striatum (Volkow et al., 2004). This study demonstrates the law of effect, with the decreased activity of the OFC and CG affecting one's ability to reassign value to drugs, hence facilitating the continued reinforcement value of drugs. This also demonstrates the bidirectional interaction of cortical and subcortical areas in motivating drug behaviour (dual process model), with the reduced activity of the orbitofrontal cortex and anterior cingulate gyrus (cortical) resulting in reduced activation of dopamine receptors in parts of the reward centre (subcortical).

Together, these studies reveal the influence of previously discussed mechanisms, involving dopamine, that motivate drug use and addiction.

Treatment
The use and abuse of illicit drugs comes at a serious cost to society, but perhaps more importantly, to the health and wellbeing of the individual. The illegal nature of the drugs also adds another level of complexity to approaching treatment. There can be fear and concern over legal ramifications or investigation after admitting to using or seeking help for illicit drug use. A huge obstacle to treatment can just simply be getting people willing to seek help, or to feel like they are safe when doing so. The good news is there are many resources and support services available for those seeking help with drug use or abuse (see external links at the bottom of the page for more information).

Research on treatments for illicit drug use tend to focus more on pharmacological strategies, as the more "hard" drugs (heroin, amphetamines, "ice") can be mediated more by physiological rather than psychological drives, especially in the context of addiction. This research also tends to use animal models, as there are ethical concerns when conducting research on humans using highly addictive substances.

Pharmacological treatment for illicit drug use include research on substances that can block the "rewarding" effects of the drugs, usually through blocking dopamine receptors. For example, one study looked at the influence of a dopamine re-uptake inhibitor called N-substituted benztropine (BZT) on rewarding effects of amphetamine use (Velazquez-Sanchez, Ferragud, Renau-Piqueras & Canales, 2011). BZT works by binding to dopamine transporters in the pre-synaptic neuron, stopping dopamine from being pumped into the synaptic cleft and binding to dopamine receptors, which in turn means that the "pleasure" message fails to be transmitted to other neurons or brain areas. The study found that the use of BZT had two effects. When it was administered after the drug, it blocked the dopamine transporter, resulting in a reduced reward response from administering the drug. When BZT was administered during abstinence it blocked the re-uptake of dopamine that had already been pumped into the synapse, allowing the brain to "normalise" the amount of dopamine transmission (Velazquez-Sanchez et al., 2011). This approach directly targets the dopamine levels before it can activate the reward centre or cortical areas. This approach also works by reducing the rewarding effects of the drugs, thereby reducing the reinforcement value of taking drugs; acting on the law of effect and operant conditioning to reduce the occurrence of drug-taking behaviour.

Alcohol and Nicotine
Alcohol is perhaps the most commonly consumed drug. Like other drugs alcohol also increases dopamine levels in the brain. One study used PET scans to measure the levels of dopamine in the brains of six humans after consuming either orange juice or ethanol (Boileau et al., 2003). Results indicated much higher levels of dopamine in the nucleus accumbens of those who consumed ethanol compared to those who consumed orange juice. The researchers also concluded that alcohol's ability to increase dopamine levels mediates its reinforcing effects, making alcohol addictive (Boileau et al., 2003).

The harmful effects of smoking cigarettes and tobacco are well known, however this knowledge alone is often not enough to reduce smoking behaviour. This is in part due to the addictive nature of nicotine, a chemical in tobacco. Like other drugs, nicotine works mostly on dopaminergic pathways. One specific pathway that nicotine works on is the pathway from the ventral tegmental area to the prefrontal cortex, and striatal structures, like the nucleus accembens (De Biasi & Dani, 2011). These structures are involved in the brain's reward centre, and also constitute elements of the dual process model; cortical and subcortical structures integrating information to generate motivation and guide motivated behaviour.

Nicotine's effect on dopamine levels in the brain have been established by early studies. For example, in Di Chiara and Imperato's (1988) study, freely moving rats were administered doses of nicotine. After, levels of dopamine in the nucleus accumbens (NA) were measured using brain dialysis. They found that dopamine levels increased by 100% in the NA over a 2 hour period following the nicotine was administered. Di Chiara and Imperato (1988) concluded that nicotine's ability to stimulate the increased production of dopamine in the NA could be a fundamental property of the drug that makes it more likely to be abused. The increased dopamine in the NA results in a strong sense of reward or pleasure, reinforcing the behaviour that led to the reward (smoking).

Treatment
Treatment for nicotine addiction varies significantly and is highly dependent on the individual. Some go cold-turkey, while others try hypnotherapy. One strategy of nicotine addiction treatment focuses on conditioning. As the Law of Effect (Thorndike, 1911) and operant conditioning suggest, behaviour that leads to a pleasurable result (the activation of the rewards centre) is more likely to be repeated. Also, as Olds and Milner (1954) found, one tends to return to or seek out the conditions and environment preceding the behaviour leading to the pleasurable experience, therefore developing cues for the possibility of reward.

Bupropion is an antidepressant that blocks the re-uptake of dopamine, which means that there are higher levels of dopamine in the brain. Benowitz (2008) has suggested that taking Bupropion could simulate the effects of nicotine, by having more dopamine in the brain. Other research on rats has also found that low doses of Bupropion actually blocks dopamine receptors, meaning that the "pleasure" message cannot be relayed to the reward centre or cortical areas, therefore reducing the reinforcing effect of smoking (Cryan, Bruijnzeel, Skjei & Markou, 2003). Although this research was not conducted on humans, this is a promising treatment option for those who may need pharmacological help to break free of conditioning.

Case Study

Brian works in a very stressful job, one which he does not enjoy. When things get too much for him, he has the overwhelming desire to go outside and smoke a cigarette. One of his friends offered one to him 1 year ago when they noticed he was having a bad day and he hasn't been able to stop since then. Although he knows smoking is bad for his health, and is an expensive habit, he struggles to push away the desire and usually gives in. He wants to quit smoking, but can't seem to quit for more than 2 days.

~ What's going on?

From the first cigarette, the nicotine in the tobacco triggered an increase in the levels of dopamine in Brian's nucleus accumbens, the brain structure that produces pleasure. This pleasure was then relayed to the prefrontal cortex so that the pleasure sensation would be brought to conscious awareness.

Since smoking produced an experience of pleasure, Brian now associates smoking with pleasure, which means that smoking behaviour will be more likely in the future. Since Brian smoked a cigarette because he was stressed, stress has now become a cue for the desire to smoke a cigarette. Whenever Brian is in a stressful situation or headspace, he has a strong desire to smoke.

Test your knowledge!
{Which brain structure is considered to be the "reward centre"? - Hypothalamus - Amygdala + Striatum - Reticular Formation - Prefrontal Cortex
 * type=""}

{The influence of dopamine on brain structures is best explained by the _________ approach. - Humanistic - Evolutionary - Sociocultural + Biological
 * type=""}

{Research has found that cocaine decreases the levels of dopamine in the brain. - True + False
 * type=""}

{The dopamine re-uptake inhibitor N-substituted benztropine (BZT) binds to which site? - Synapse - Dopamine receptor + Dopamine transporter - Dopamine pathway
 * type=""}

Conclusion
As research has suggested, dopamine plays a major part in drug use and addiction. It is critical in activating the reward centre of the brain, and also plays a part in bringing the pleasure into consciousness, by relaying the message into cortical areas. Dopamine's ability to generate pleasure lends its influence to the law of effect and operant conditioning, aiding in the reinforcement of drug use. There are a number of strategies that can be implemented when trying to combat addictive behaviour. Taking medication to block dopamine receptors has been found to help with amphetamine addiction and medication that blocks re-uptake of dopamine has been found to help with nicotine addiction. All of these options ultimately lead back to conditioning, and all attempt to reduce the reinforcing value of drug use.