Wednesday, July 11, 2012

Brain Circuits and Addiction

Brain circuits and drug use

What is the nature of addiction?

Amy Winehouse was a terrific talent and one of the favorite recording artists of all time. She also struggled with substance abuse. To what extent remains largely unknown but her death has fueled debate as to the precise nature of drug addiction and how it should be addressed by society as a whole.

In other words, why do some people behave in the often self-destructive manner in which they do? And why are people addicted to drugs in the first place?  How, if at all, might they be helped?

Now, you might think that this is a spectacularly hard task to delve into the neuroscience of addiction try to shed some light. Surely, drugs of abuse (such as amphetamines, cocaine, opiates, alcohol and nicotine) have a broad range of actions that are wholly dissimilar from each other? Well, that is partly true, but when it comes to their addictive properties, they have more in common than you might think.

What constitutes addiction?

Addiction, as most will know, develops as a result of chronic exposure to a particular substance. People who are addicted to a drug show similar patterns of behaviour. These include:

1. A compulsion to seek the drug

2. An inability to control the amount of drug consumption

3. A negative emotional state when subjected to periods of withdrawal

Neuroscientists have sought to understand the neural mechanisms underlying these behaviours for generations and emerging from these studies is the concept of the ‘reward circuit’ that seems to be involved in the development and maintenance of drug addiction.  In fact, research on the medial forebrain pleasure circuit may be entering a golden age of discovery.

Now, a lot of neuroscience (indeed any science) is about gradually building up a picture from fragments of information. In most cases, that information may not even come from human subjects but from animal models. That means that current ideas regarding drug addiction are far from unequivocal, but from looking at the correlations between how the rodent brain and human brain are altered during the development of drug addiction, we can make careful assumptions about what might be the general rule.
You see, the brain behaves a little bit like a factory, with different departments responsible for producing a certain sort of feeling or behaviour. This means that there are anatomically distinct areas that are concerned with happiness, memory, movement and so on. This is (as ever) an oversimplification, as it is usually the concerted action of several brain regions that lead to emergence of a particular thought or action. However, it is useful to think of the brain in this way, particularly when analysing how brain circuits are altered in drug users.

The reward circuit

The reward circuit consists of several brain regions that are heavily interconnected; each with distinct – but related – functionality. These include the nucleus accumbens (a brain region that is extremely well documented for its involvement in drug addiction), the ventral tegmental area, the amygdala, the prefrontal cortex, the hippocampus and the insula, among others.

Dysfunction in each of these areas has been implicated in the onset and maintenance of drug-addiction, each area being responsible for a slightly different facet of the drug-addicted mental state.

The nucleus accumbens: pleasure

Now, the nucleus accumbens is known as the reward center of the brain. Largely because in various different experimental paradigms, subjects that report that they are experiencing reward show increased activity in this area. This can be whilst taking drugs of abuse or simply eating, engaging in sexual activity or indeed anything associated with pleasurable reward.

All drugs of abuse raise the level of a chemical known as dopamine in the nucleus accumbens and it is this elevation in dopamine (initiated in different ways by different drugs) that is responsible for the feeling of euphoria associated with drug intake.

However, persistent activation of the nucleus accumbens leads to the development of drug addiction, primarily due to persistent changes in the level of dopamine, which leads to an alteration in how people respond to otherwise rewarding stimuli. Put simply, after disruption of the dopamine levels in the nucleus accumbens, people get less satisfied with things that aren’t their drugs of choice. Furthermore, people derive progressively more pleasure from the drug in question, exacerbating the effect.

The amygdala: fear

On the flip side of the coin, the amygdala is a region of the brain situated right next to the nucleus accumbens but is often associated with feelings of fear and anxiety.
As opposed to the positive reinforcement created by the nucleus accumbens, it is during withdrawal that the amygdala seems to have its largest role. Basically, as access to the drug is taken away, stress-related hormones are increased in the amygdala which can lead (at least partially) to the negative feeling associated with withdrawal.

The hippocampus: memory

The hippocampus is an area of the brain that is associated with learning and memory as well as the ability to perform tasks requiring spatial navigation, such as finding your way around a building. It is also important for ‘contextual-conditioning’, meaning that it enables the mind to establish links between an environmental cue (a nightclub, for example) and a memory (such as taking a drug.)

Activation of the hippocampus is implicated in initiating cue-induced drug-seeking behaviour. Indeed, it has been shown that cue-induced craving of drugs (eg. the feeling of needing a drink in a pub or a cigarette with a cup of coffee) is associated with an increase in activity in the hippocampus (as well as the amygdala) in humans, indicating that normal memory function may be being encroached upon by drugs of abuse.

The prefrontal cortex: decision

The prefrontal cortex consists of several subdivisions including the orbitofrontal cortex and dorsolateral prefrontal cortex. These areas have a variety of different functions but are often described as being imperative in carrying out decision-making processes in response to internal/external-cues, a process known as executive function.

It is believed that the activity of the prefrontal cortex is disrupted in subjects who are addicted to drugs. This may go some way to explaining why drug users often make poor decisions regarding drug intake (ie. pursuing a drug whilst fully aware of the negative impact drug intake will have on them and the people around them.)

What goes on in the brain of a drug addict

As complicated as that may have sounded, it represents a gross oversimplification of what actually goes on in the mind of a drug addict. I simply wanted to introduce you to some of the concepts that are emerging as a result of neuroscientific research and give you a flavor of what is to come in future posts. As I move through my journey into drug addiction, I will make constant references to the reward circuit and its components and so an introduction was necessary to familiarise you with the brain’s machinery. -- Dr. Paul

Dr. Paul is a graduate from the University of Bristol and the author of Dr Paul’s Brain Talk, a neuroscience-related magazine. Dr. Paul believes that over the coming decades, neuroscience research will begin to have a greater impact on our lives and he aims to bring the findings of this fascinating field to the general public, in words they can understand.

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